Lis-1 (DLis-1, CG8440) is the Drosophila ortholog of human LIS1 (PAFAH1B1), a WD40 beta-propeller protein with an N-terminal LisH dimerization motif that binds and regulates cytoplasmic dynein. Lis1 co-purifies with dynein and dynactin, promotes their association and their recruitment to cargoes such as mRNA localization complexes, the nuclear surface, spindle poles and kinetochores, and colocalizes with them on centrosomes, spindle and kinetochore microtubules and the oocyte cortex. Through dynein it drives nuclear positioning (oocyte nucleus migration that patterns the dorsal-ventral axis; nucleus-centrosome coupling in spermatocytes), centrosome separation and bipolar spindle assembly in neuroblasts, poleward stripping of checkpoint proteins from kinetochores, minus-end-directed mRNA transport in embryos, and axonal and dendritic transport in neurons. Loss of Lis1 is lethal and causes defects in germline cyst divisions, fusome integrity, oocyte determination and growth, spermatogenesis, neuroblast proliferation, dendrite arborization, border cell migration and germline stem cell maintenance. The fly protein is highly conserved with mammalian LIS1 but does not bind the Drosophila PAF-AH alpha subunit homolog.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IEA GO_REF:0000104 | ACCEPT | Summary: Electronic (UniRule) transfer of establishment of mitotic spindle orientation to Drosophila Lis-1. Reason: Cortical dynein pulling on astral microtubules, which orients the mitotic spindle, is a conserved LIS1-dependent function; Drosophila Lis1 is required for spindle assembly and centrosome positioning in neuroblasts, and loss of Lis1 phenocopies dynein. The UniRule transfer is consistent with the fly biology and the human ortholog. Supporting Evidence: PMID:16107559 We conclude that Lis1 has a critical role in correct spindle assembly by regulating centrosome separation, focusing of spindle poles, centrosome attachment, and centrosome number and/or centrosome integrity in larval neuroblasts. file:DROME/Lis-1/Lis-1-uniprot.txt Positively regulates the activity of the minus-end directed |
| GO:0000776 kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: kinetochore localization, inherited from the LIS1/NudF clade. Reason: Drosophila Lis1 is directly observed at unattached/prometaphase kinetochores in neuroblasts, S2 cells and spermatocytes, in agreement with this phylogenetic inference. Supporting Evidence: PMID:16105886 This localisation depends on the dynein-dynactin complex and Lis1 which also localise to unattached kinetochores. PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores |
| GO:0000776 kinetochore | IDA PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | ACCEPT | Summary: Lis1 colocalizes with dynactin, dynein and the checkpoint protein Rod on prometaphase kinetochores of larval neuroblasts. Reason: Direct imaging evidence of kinetochore localization; kinetochore dynein/Lis1 transports checkpoint proteins poleward. Supporting Evidence: PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores PMID:16107559 In summary, Lis1/dynactin/dynein coimmunoprecipitate, localize to centrosome/spindle poles, and are transiently colocalized with the checkpoint protein Rod on prometaphase kinetochores before enrichment on kMTs. |
| GO:0000776 kinetochore | IDA PMID:22764052 Regulation of dynein localization and centrosome positioning... | ACCEPT | Summary: LIS-1 colocalizes with dynactin at kinetochores of prometaphase spermatocytes. Reason: Direct localization evidence in male meiotic cells, consistent with neuroblast data. Supporting Evidence: PMID:22764052 In prometaphase spermatocytes, LIS-1 colocalized with dynactin at kinetochores |
| GO:0000922 spindle pole | IDA PMID:22764052 Regulation of dynein localization and centrosome positioning... | ACCEPT | Summary: LIS-1 concentrates at meiotic spindle poles in spermatocytes and recruits dynein-dynactin there. Reason: Direct localization; Lis1 is required for dynein-dynactin recruitment to spindle poles. Supporting Evidence: PMID:22764052 Throughout both meiotic divisions, LIS-1 concentrates at spindle poles PMID:22764052 LIS-1 colocalizes with dynein-dynactin at the nuclear surface and spindle poles of male germ cells and is required for recruiting dynein-dynactin to these sites. |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to spindle pole. Reason: Consistent with direct observation of Lis1 at mitotic (neuroblast) and meiotic (spermatocyte) spindle poles. Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Cytoplasm, cytoskeleton, spindle pole. Chromosome, PMID:22764052 Throughout both meiotic divisions, LIS-1 concentrates at spindle poles |
| GO:0005515 protein binding | IPI PMID:21041636 Lissencephaly-1 controls germline stem cell self-renewal thr... | MODIFY | Summary: Co-immunoprecipitation of tagged Lis1 with the SMAD protein Mad in S2 cells. Reason: Generic protein binding is uninformative. The cited study shows reciprocal co-immunoprecipitation of Lis1 and Mad and argues for a direct association that stabilises Mad and facilitates its phosphorylation; SMAD binding captures this specific, evidence-backed partner class. This is a lineage-restricted observation (BMP/GSC context), not the core dynein-regulator function. Proposed replacements: SMAD binding Supporting Evidence: PMID:21041636 Mechanistically, Lis1 binds directly to and stabilizes the SMAD protein Mothers against decapentaplegic (Mad), facilitates its phosphorylation, and thereby regulates BMP signaling. PMID:21041636 Interestingly, Flag-tagged Lis1 and HA-tagged Mad immunoprecipitated each other down in the S2 cells |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: cytoplasm. Reason: Lis1 is a cytoplasmic dynein regulator found on microtubules, centrosomes, the cortex and the nuclear surface; cytoplasm is correct though general. Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Positively regulates the activity of the minus-end directed |
| GO:0005737 cytoplasm | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule: cytoplasm. Reason: Correct, general location for a cytoplasmic dynein regulator. Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Positively regulates the activity of the minus-end directed |
| GO:0005813 centrosome | IDA PMID:22764052 Regulation of dynein localization and centrosome positioning... | ACCEPT | Summary: LIS-1 is perinuclear and focuses at centrosomes during meiotic prophase in spermatocytes. Reason: Direct localization evidence; Lis1 is needed for centrosome-nucleus attachment. Supporting Evidence: PMID:22764052 Perinuclear LIS-1 becomes focused at centrosomes during prophase I and II |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to centrosome. Reason: Supported by direct fly localization data (spermatocytes, neuroblasts). Supporting Evidence: PMID:22764052 Perinuclear LIS-1 becomes focused at centrosomes during prophase I and II PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores |
| GO:0005828 kinetochore microtubule | IDA PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | KEEP AS NON CORE | Summary: Lis1 and dynactin distribute along kinetochore microtubules during metaphase in neuroblasts. Reason: Colocalization with Rod along kMTs reflects dynein-driven poleward stripping of kinetochore cargo; a valid but transient, mitosis-specific location. Supporting Evidence: PMID:16107559 Both proteins were colocalized with Rod on prometaphase kinetochores ( Figure 7B and unpublished data), and distributed along kMTs during metaphase |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoskeleton. Reason: General but correct; Lis1 associates with microtubules and microtubule organizing centres. Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Cytoplasm, cytoskeleton, spindle pole. Chromosome, |
| GO:0005869 dynactin complex | IDA PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | MODIFY | Summary: Lis1 co-immunoprecipitates with dynactin (Glued) and dynein and colocalizes with them. Reason: The co-IP supports physical association (captured by dynein complex binding), but LIS1 is not a stoichiometric subunit of dynactin; it is a transiently bound dynein regulator. Consistent with the human LIS1 review, the complex association is better represented by the parent microtubule associated complex. Proposed replacements: microtubule associated complex Supporting Evidence: PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores |
| GO:0005875 microtubule associated complex | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule: microtubule associated complex. Reason: Lis1 is part of dynein-regulatory assemblies (Lis1/NudE/dynein/dynactin) on microtubules; this general complex term matches the human LIS1 review. Supporting Evidence: PMID:16107559 In summary, Lis1/dynactin/dynein coimmunoprecipitate, localize to centrosome/spindle poles, and are transiently colocalized with the checkpoint protein Rod on prometaphase kinetochores before enrichment on kMTs. |
| GO:0005938 cell cortex | IDA PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | ACCEPT | Summary: DLis-1 shows cortical localization in the oocyte, independent of microtubules. Reason: Direct immunostaining evidence; cortical dynein/Lis1 is a conserved anchoring and force-generating site. Supporting Evidence: PMID:10559989 Immunostaining of DLis-1 protein reveals a cortical localization that is independent of microtubules. |
| GO:0006886 intracellular protein transport | IMP PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | KEEP AS NON CORE | Summary: Lis1 is required for poleward transport of the checkpoint protein Rod off kinetochores. Reason: Lis1 regulates the dynein motor that transports kinetochore proteins; the annotation is correct in the sense of dynein-mediated protein transport, but it is a specific cargo context rather than the core activity. Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. PMID:16107559 In contrast, Lis1 – mutant neuroblasts lacked poleward GFP-Rod streaming and thus showed persistent GFP-Rod kinetochore localization during metaphase and anaphase |
| GO:0007017 microtubule-based process | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule: microtubule-based process. Reason: Correct high-level process for a dynein regulator. Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Positively regulates the activity of the minus-end directed |
| GO:0007097 nuclear migration | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | ACCEPT | Summary: DLis-1 is required for nuclear positioning in the oocyte and nuclear localization in the developing nervous system. Reason: Core conserved function of the LIS1/NudF family; Lis1 acts with dynein, BicD and Egl in nuclear positioning. The more specific GO:0030473 is also annotated. Supporting Evidence: PMID:10559989 DLis-1 is further required for nurse-cell-to-oocyte transport during oocyte growth, and for the positioning of the nucleus in the oocyte. PMID:10559989 DLis-1 and Bic-D are further required for nuclear localization in the developing nervous system |
| GO:0007283 spermatogenesis | IMP PMID:22764052 Regulation of dynein localization and centrosome positioning... | KEEP AS NON CORE | Summary: Lis-1 male-sterile allele shows centrosome positioning, nucleus-basal body and Nebenkern defects during spermatogenesis. Reason: Valid developmental involvement that reflects dynein regulation (centrosome positioning, nucleus-centrosome coupling) in male germ cells; non-core. Supporting Evidence: PMID:22764052 We found that centrosomes do not properly detach from the cell cortex at the onset of meiosis in most Lis-1 spermatocytes; centrosomes that do break cortical associations fail to attach to the nucleus. PMID:22764052 We present a model in which Lis-1 and asun cooperate to regulate dynein localization and centrosome positioning during Drosophila spermatogenesis. |
| GO:0007294 germarium-derived oocyte fate determination | IGI PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: Lis1 genetically interacts with Bic-D in oocyte determination. Reason: Oocyte determination depends on dynein-mediated minus-end transport directed by BicD/Egl, which Lis1 supports; developmental consequence of the core function. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. |
| GO:0007294 germarium-derived oocyte fate determination | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: DLis-1 is required for oocyte determination. Reason: As above: developmental consequence of Lis1-dependent dynein transport. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. |
| GO:0007298 border follicle cell migration | IMP PMID:22808215 Microtubules and Lis-1/NudE/dynein regulate invasive cell-on... | KEEP AS NON CORE | Summary: Lis-1 is required cell-autonomously for border cell migration. Reason: RNAi/mosaic screen hit with NudE and dynein; a dynein-dependent cell migration process, non-core. Supporting Evidence: PMID:22808215 A screen of 67 genes encoding microtubule interacting proteins uncovered cell autonomous requirements for Lis-1, NudE and Dynein in border cell migration. |
| GO:0007300 ovarian nurse cell to oocyte transport | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: DLis-1 is required for nurse-cell-to-oocyte transport. Reason: Reflects dynein-dependent transport into the oocyte; valid developmental role, non-core. Supporting Evidence: PMID:10559989 DLis-1 is further required for nurse-cell-to-oocyte transport during oocyte growth, and for the positioning of the nucleus in the oocyte. |
| GO:0007312 oocyte nucleus migration involved in oocyte dorsal/ventral axis specification | IMP PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | ACCEPT | Summary: DLis1 mutations misposition the oocyte nucleus, disrupting gurken localization and dorsal/ventral patterning. Reason: This is the Drosophila instance of the conserved LIS1 nuclear-migration function, with genetic interactions with Glued and Dhc supporting a dynein-based mechanism. Supporting Evidence: PMID:10993674 DLis1 mutations affect the localization of gurken mRNA and protein in the oocyte. These defects are correlated with incorrect positioning of the oocyte nucleus, suggesting that DLis1 is required for nuclear migration. PMID:10993674 DLis1 shows genetic interactions with the Glued and Dynein heavy chain subunits of the dynein/dynactin complex, supporting the idea that the Lis1 family of proteins plays a role in microtubule motor-based nuclear motility. |
| GO:0007405 neuroblast proliferation | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | KEEP AS NON CORE | Summary: Lis1 null clones fail to proliferate in neuroblasts. Reason: Consequence of mitotic dynein functions (centrosome separation, spindle assembly); valid but non-core. Supporting Evidence: PMID:11056531 Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. |
| GO:0008088 axo-dendritic transport | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | ACCEPT | Summary: Lis1 is required for axonal transport in mushroom body neurons. Reason: Dynein-regulator role in neuronal transport, phenocopied by Dhc64C mutants; consistent with conserved retrograde transport function. Supporting Evidence: PMID:11056531 Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. PMID:11056531 Analogous mosaic analysis shows that neurons containing a mutated cytoplasmic-dynein heavy chain (Dhc64C) exhibit phenotypes similar to Lis1 mutants. |
| GO:0008090 retrograde axonal transport | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: retrograde axonal transport. Reason: Supported by Drosophila experimental data (Dscam restriction, Neuroglian retrograde trafficking) and by the human ortholog; LIS1 regulates dynein, the retrograde motor. Supporting Evidence: PMID:28837701 In summary, our results suggest that Lis-1 has a function in GF synapse development and that both Lis1 and dynactin play a role in Nrg retrograde trafficking. PMID:18946501 Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport. |
| GO:0008090 retrograde axonal transport | IMP PMID:18946501 Dynein-dynactin complex is essential for dendritic restricti... | ACCEPT | Summary: Lis1 mutations disrupt dynein-dynactin-mediated exclusion of Dscam[TM1] from axons. Reason: Lis1 was recovered with dynactin subunits in a forward screen; the study concludes dynein-dynactin removes Dscam from axons by retrograde transport. Supporting Evidence: PMID:18946501 We identified three mutations in the known components of dynein-dynactin complex (Lis1, p24 and Dynamitin) that all affect Dscam dendritic targeting. PMID:18946501 Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport. |
| GO:0008090 retrograde axonal transport | IMP PMID:28837701 Lissencephaly-1 dependent axonal retrograde transport of L1-... | ACCEPT | Summary: Lis1 knockdown blocks retrograde trafficking of Neuroglian in giant fiber axons. Reason: Direct IMP evidence for a role in retrograde axonal transport. Supporting Evidence: PMID:28837701 In summary, our results suggest that Lis-1 has a function in GF synapse development and that both Lis1 and dynactin play a role in Nrg retrograde trafficking. |
| GO:0008104 intracellular protein localization | IGI PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: Genetic interaction with Dhc64C in protein localization in the oocyte. Reason: Reflects dynein-dependent localization of oocyte determinants; valid, non-core and broad. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. |
| GO:0008104 intracellular protein localization | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: DLis-1 required for localization of oocyte-specific factors. Reason: Consequence of Lis1-dependent dynein transport; non-core. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. |
| GO:0008104 intracellular protein localization | IMP PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | KEEP AS NON CORE | Summary: DLis1 mutations affect Gurken protein localization. Reason: Gurken mislocalization is secondary to oocyte nucleus mispositioning; non-core. Supporting Evidence: PMID:10993674 DLis1 mutations affect the localization of gurken mRNA and protein in the oocyte. These defects are correlated with incorrect positioning of the oocyte nucleus, suggesting that DLis1 is required for nuclear migration. |
| GO:0008298 intracellular mRNA localization | IMP PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | ACCEPT | Summary: DLis1 mutations affect gurken mRNA localization in the oocyte. Reason: In this study gurken mislocalization correlates with oocyte nucleus mispositioning, but Lis1 is independently shown to be part of the dynein-based mRNA localization machinery (PMID:23918939), so intracellular mRNA localization is an accepted Lis1 process. Supporting Evidence: PMID:10993674 DLis1 mutations affect the localization of gurken mRNA and protein in the oocyte. These defects are correlated with incorrect positioning of the oocyte nucleus, suggesting that DLis1 is required for nuclear migration. |
| GO:0008298 intracellular mRNA localization | IMP PMID:23918939 Lissencephaly-1 promotes the recruitment of dynein and dynac... | ACCEPT | Summary: Lis1 is recruited to RNA localization signals and required for minus-end transport of localizing mRNAs in embryos. Reason: Direct biochemical and imaging evidence that Lis1 recruits dynein-dynactin to mRNA cargoes; dynein-mediated mRNA localization is a well-established Lis1 role in flies. Supporting Evidence: PMID:23918939 We identified the protein Lissencephaly-1 (Lis1) and found that minus-end travel distances of localizing transcripts are dramatically reduced in lis1 mutant embryos. PMID:23918939 Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. |
| GO:0010970 transport along microtubule | IMP PMID:23918939 Lissencephaly-1 promotes the recruitment of dynein and dynac... | ACCEPT | Summary: Lis1 promotes minus end-directed microtubule transport of mRNA cargo. Reason: Direct evidence that Lis1 promotes dynein-based transport along microtubules. Supporting Evidence: PMID:23918939 We identified the protein Lissencephaly-1 (Lis1) and found that minus-end travel distances of localizing transcripts are dramatically reduced in lis1 mutant embryos. PMID:23918939 Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: microtubule cytoskeleton. Reason: Lis1 localizes to centrosomes, spindle microtubules and kinetochore microtubules. Supporting Evidence: PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores |
| GO:0016319 mushroom body development | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | KEEP AS NON CORE | Summary: Lis1 mosaic analysis in mushroom body neurons. Reason: Developmental consequence of dynein-dependent neuroblast division and neurite growth; non-core. Supporting Evidence: PMID:11056531 Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. PMID:11056531 Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. |
| GO:0016358 dendrite development | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | KEEP AS NON CORE | Summary: Lis1 is cell-autonomously required for dendritic growth, branching and maturation. Reason: Developmental consequence of dynein regulation; non-core. Supporting Evidence: PMID:11056531 Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. |
| GO:0019827 stem cell population maintenance | IDA PMID:21041636 Lissencephaly-1 controls germline stem cell self-renewal thr... | KEEP AS NON CORE | Summary: Lis1 controls ovarian germline stem cell self-renewal. Reason: Supported by clonal analysis; tissue-specific role, possibly via BMP signalling and E-cadherin; non-core. Supporting Evidence: PMID:21041636 Lis1 mutant GSCs are lost faster than control GSCs because of differentiation but not because of cell death, indicating that Lis1 controls GSC self-renewal. |
| GO:0030286 dynein complex | IDA PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | MODIFY | Summary: Lis1 co-immunoprecipitates with dynein heavy chain and colocalizes with dynein. Reason: The data show physical association (already captured by dynein complex binding, GO:0070840, from the same paper) rather than stoichiometric subunit membership. LIS1 is a transient dynein regulator; the human LIS1 review uses microtubule associated complex for complex membership. Proposed replacements: microtubule associated complex Supporting Evidence: PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits |
| GO:0030286 dynein complex | IEA GO_REF:0000117 | MODIFY | Summary: ARBA: dynein complex. Reason: LIS1 is a transiently associated regulator rather than a dynein subunit; microtubule associated complex (the parent, and the term used for the human ortholog) plus dynein complex binding better represent this. Proposed replacements: microtubule associated complex Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt Positively regulates the activity of the minus-end directed |
| GO:0030381 chorion-containing eggshell pattern formation | IMP PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | KEEP AS NON CORE | Summary: DLis1 mutations cause partial ventralization of the eggshell. Reason: Downstream consequence of oocyte nucleus mispositioning and Gurken mislocalization; non-core. Supporting Evidence: PMID:10993674 In this study we show that mutations in the Drosophila Lissencephaly1 (DLis1) gene result in partial ventralization of the eggshell. |
| GO:0030424 axon | IDA PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | ACCEPT | Summary: Lis1 is expressed in nervous system and present in axons. Reason: Consistent with its role in axonal transport; the curator had full text of expression data. Supporting Evidence: PMID:11056531 Here we show that Drosophila Lis1 is highly expressed in the nervous system. PMID:11056531 Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. |
| GO:0030425 dendrite | IDA PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | ACCEPT | Summary: Lis1 is present in dendrites of mushroom body neurons. Reason: Consistent with its cell-autonomous role in dendrite growth. Supporting Evidence: PMID:11056531 Here we show that Drosophila Lis1 is highly expressed in the nervous system. PMID:11056531 Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. |
| GO:0030426 growth cone | IDA PMID:25694447 Drosophila CLIP-190 and mammalian CLIP-170 display reduced m... | ACCEPT | Summary: Endogenous Lis1 is enriched in growth cones of primary neurons. Reason: Direct immunolocalization. Supporting Evidence: PMID:25694447 We found that fly Lis1 distributes throughout GCs |
| GO:0030473 nuclear migration along microtubule | IGI PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | ACCEPT | Summary: Genetic interaction of DLis1 with Glued in nuclear migration. Reason: DLis1 interacts genetically with dynactin and dynein subunits in oocyte nuclear migration, supporting motor-based nuclear motility along microtubules. Core conserved function. Supporting Evidence: PMID:10993674 DLis1 shows genetic interactions with the Glued and Dynein heavy chain subunits of the dynein/dynactin complex, supporting the idea that the Lis1 family of proteins plays a role in microtubule motor-based nuclear motility. PMID:10993674 DLis1 mutations affect the localization of gurken mRNA and protein in the oocyte. These defects are correlated with incorrect positioning of the oocyte nucleus, suggesting that DLis1 is required for nuclear migration. |
| GO:0030473 nuclear migration along microtubule | IGI PMID:10993674 The Drosophila Lissencephaly1 (DLis1) gene is required for n... | ACCEPT | Summary: Genetic interaction of DLis1 with Dynein heavy chain in nuclear migration. Reason: As above; core conserved function. Supporting Evidence: PMID:10993674 DLis1 shows genetic interactions with the Glued and Dynein heavy chain subunits of the dynein/dynactin complex, supporting the idea that the Lis1 family of proteins plays a role in microtubule motor-based nuclear motility. |
| GO:0030513 positive regulation of BMP signaling pathway | IDA PMID:21041636 Lissencephaly-1 controls germline stem cell self-renewal thr... | KEEP AS NON CORE | Summary: Lis1 is required for BMP signalling in ovarian germline stem cells and stabilises Mad. Reason: Single-study, tissue-specific mechanism (Lis1 binds and stabilises Mad); plausible but not part of the conserved dynein-regulator function. Retained as non-core. Supporting Evidence: PMID:21041636 Mechanistically, Lis1 binds directly to and stabilizes the SMAD protein Mothers against decapentaplegic (Mad), facilitates its phosphorylation, and thereby regulates BMP signaling. PMID:21041636 The Lis1 mutant GSCs exhibit reduced BMP signaling activity, and Lis1 interacts genetically with the BMP pathway components in the regulation of GSC maintenance. |
| GO:0030706 germarium-derived oocyte differentiation | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Lis1 required in the germline for oocyte differentiation. Reason: Developmental consequence; non-core. Supporting Evidence: PMID:10498683 Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. |
| GO:0030716 oocyte fate determination | IGI PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: Genetic interaction with Egalitarian in oocyte fate determination. Reason: Consistent with Lis1 acting with Egl/BicD/dynein in oocyte determination; non-core. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. |
| GO:0030723 ovarian fusome organization | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Lis1 required for fusome integrity in ovarian germline cysts. Reason: Supported by mosaic analysis; the fusome is a microtubule/membrane-cytoskeletal organelle. Non-core. Supporting Evidence: PMID:10498683 Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. |
| GO:0031616 spindle pole centrosome | IDA PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | ACCEPT | Summary: Lis1 colocalizes with dynein/dynactin at centrosomes of spindle poles in neuroblasts. Reason: Direct colocalization evidence. Supporting Evidence: PMID:16107559 Furthermore, we show that Lis1/dynactin/dynein physically associate and colocalize on centrosomes, spindle MTs, and kinetochores PMID:16107559 In summary, Lis1/dynactin/dynein coimmunoprecipitate, localize to centrosome/spindle poles, and are transiently colocalized with the checkpoint protein Rod on prometaphase kinetochores before enrichment on kMTs. |
| GO:0034501 protein localization to kinetochore | IMP PMID:16105886 Distinct mechanisms govern the localisation of Drosophila CL... | KEEP AS NON CORE | Summary: Lis1 is required for CLIP-190 localization to unattached kinetochores. Reason: Supported by the hierarchical dependency in S2 cells; reflects Lis1/dynein-dynactin recruitment of kinetochore components; non-core. Supporting Evidence: PMID:16105886 This localisation depends on the dynein-dynactin complex and Lis1 which also localise to unattached kinetochores. |
| GO:0042052 rhabdomere development | IMP PMID:21943192 New dystrophin/dystroglycan interactors control neuron behav... | KEEP AS NON CORE | Summary: Loss of Lis1 shortens rhabdomeres in a screen for dystrophin/dystroglycan interactors. Reason: Screen-level phenotype; developmental consequence; non-core. Supporting Evidence: PMID:21943192 loss of SP2353, Grh, Nrk, capt, CG34400, vimar, Lis1 and Cam cause shortened rhabdomere lengths |
| GO:0043025 neuronal cell body | IDA PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | ACCEPT | Summary: Lis1 is present in neuronal cell bodies. Reason: Consistent with pan-neuronal expression; located_in is appropriate. Supporting Evidence: PMID:11056531 Here we show that Drosophila Lis1 is highly expressed in the nervous system. |
| GO:0045478 fusome organization | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Lis1 required for fusome integrity. Reason: As for ovarian fusome organization; non-core. Supporting Evidence: PMID:10498683 Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | IGI PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | KEEP AS NON CORE | Summary: Lis1 and rod genetic interaction in mitotic timing. Reason: Lis1 promotes timely anaphase onset by driving dynein-dependent stripping of checkpoint proteins (Rod) from kinetochores; reducing Rod bypasses the delay. Valid, mitosis-specific, non-core. Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. PMID:16107559 In contrast, Lis1 – mutant neuroblasts lacked poleward GFP-Rod streaming and thus showed persistent GFP-Rod kinetochore localization during metaphase and anaphase |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | IMP PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | KEEP AS NON CORE | Summary: Lis1 mutants delay the metaphase/anaphase transition. Reason: As above. Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. |
| GO:0046716 muscle cell cellular homeostasis | IGI PMID:21256839 Stress and muscular dystrophy: a genetic screen for dystrogl... | UNDECIDED | Summary: Lis1 reported as a genetic interactor of dystroglycan/dystrophin in ageing muscle. Reason: The cached reference is abstract-only and does not mention Lis1; the specific phenotype underlying muscle cell cellular homeostasis cannot be verified. Deferring rather than overruling the curator. |
| GO:0046716 muscle cell cellular homeostasis | IMP PMID:21256839 Stress and muscular dystrophy: a genetic screen for dystrogl... | UNDECIDED | Summary: Lis1 mutant muscle phenotype from a genetic screen. Reason: As for the IGI row: abstract-only, Lis1-specific data not visible. |
| GO:0048135 female germ-line cyst formation | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Abnormal cyst packaging in Lis1 mutant clones. Reason: Developmental consequence; non-core. Supporting Evidence: PMID:10498683 Abnormal packaging of the cysts was observed in Lis1 mutant clones. |
| GO:0048142 germarium-derived cystoblast division | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Lis1 required for synchronized germline cell division. Reason: Consequence of mitotic dynein function in cystoblast divisions; non-core. Supporting Evidence: PMID:10498683 Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. |
| GO:0048477 oogenesis | IMP PMID:10498683 Lis1, the Drosophila homolog of a human lissencephaly diseas... | KEEP AS NON CORE | Summary: Lis1 required in the germline for oogenesis. Reason: Broad developmental process; non-core. Supporting Evidence: PMID:10498683 Analysis of ovarian Lis1 mutant clones demonstrates that Lis1 is required in the germline for synchronized germline cell division, fusome integrity and oocyte differentiation. |
| GO:0048477 oogenesis | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | KEEP AS NON CORE | Summary: DLis-1 required for oocyte determination, growth and nuclear positioning. Reason: Broad developmental process; non-core. Supporting Evidence: PMID:10559989 Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. PMID:10559989 DLis-1 is further required for nurse-cell-to-oocyte transport during oocyte growth, and for the positioning of the nucleus in the oocyte. |
| GO:0048813 dendrite morphogenesis | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | KEEP AS NON CORE | Summary: Lis1 cell-autonomously required for dendrite growth and branching. Reason: Developmental consequence of dynein regulation; non-core. Supporting Evidence: PMID:11056531 Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. |
| GO:0048813 dendrite morphogenesis | IMP PMID:18758452 Spatial control of branching within dendritic arbors by dyne... | KEEP AS NON CORE | Summary: Lis1 in dendrite branching of da neurons (dynein-dependent Rab5 endosome transport). Reason: The cached reference is abstract-only and the abstract does not mention Lis1, but the curator read the full text and the function is consistent with Lis1 as a dynein regulator (and with PMID:11056531). Deferring; non-core. Supporting Evidence: PMID:11056531 Moreover, it is cell-autonomously required for dendritic growth, branching and maturation. |
| GO:0048814 regulation of dendrite morphogenesis | IMP PMID:18758451 Dynein is required for polarized dendritic transport and uni... | KEEP AS NON CORE | Summary: Loss of Lis1 phenocopies dynein light intermediate chain mutants in da neuron dendrites. Reason: Lis1 is a dynein regulator required for polarized dendritic transport; "regulation" here reflects dynein-dependent transport rather than a signalling role. Non-core. Supporting Evidence: PMID:18758451 loss of Lis1, which interacts with dynein, phenocopies dlic21157 |
| GO:0050772 positive regulation of axonogenesis | IMP PMID:28837701 Lissencephaly-1 dependent axonal retrograde transport of L1-... | KEEP AS NON CORE | Summary: Lis1 knockdown disrupts giant fiber terminal development. Reason: Phenotype reflects dynein-dependent transport; Lis1 is not a dedicated regulator of axonogenesis. Kept as non-core. Supporting Evidence: PMID:28837701 Both RNAi-lines resulted in indistinguishable anatomical phenotypes that were similar to the hypomorphic lis1 mutants in that they disrupted GF synapse formation and its function |
| GO:0051012 microtubule sliding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: UniRule: microtubule sliding. Reason: Derived from fungal/mammalian data that LIS1 targets dynein to microtubule plus ends and may enhance dynein-mediated sliding; plausible but not demonstrated in Drosophila. Consistent with the human LIS1 review (non-core). Supporting Evidence: file:DROME/Lis-1/Lis-1-uniprot.txt May enhance dynein-mediated |
| GO:0051225 spindle assembly | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA: spindle assembly. Reason: Supported by Drosophila experimental data (bipolar spindle defects in Lis1 neuroblasts). Supporting Evidence: PMID:16107559 We conclude that Lis1 has a critical role in correct spindle assembly by regulating centrosome separation, focusing of spindle poles, centrosome attachment, and centrosome number and/or centrosome integrity in larval neuroblasts. |
| GO:0051225 spindle assembly | IMP PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | ACCEPT | Summary: Lis1 mutant neuroblasts have spindle assembly defects. Reason: Direct IMP evidence from live imaging. Supporting Evidence: PMID:16107559 We conclude that Lis1 has a critical role in correct spindle assembly by regulating centrosome separation, focusing of spindle poles, centrosome attachment, and centrosome number and/or centrosome integrity in larval neuroblasts. PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. |
| GO:0051299 centrosome separation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA: centrosome separation. Reason: Supported by Drosophila experimental data. Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. |
| GO:0051299 centrosome separation | IMP PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | ACCEPT | Summary: Lis1 mutant neuroblasts show incomplete centrosome separation. Reason: Direct IMP evidence; dynein-dependent centrosome separation is a conserved LIS1 function (also in C. elegans). Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. PMID:16107559 We conclude that Lis1 has a critical role in correct spindle assembly by regulating centrosome separation, focusing of spindle poles, centrosome attachment, and centrosome number and/or centrosome integrity in larval neuroblasts. |
| GO:0051383 kinetochore organization | IMP PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | KEEP AS NON CORE | Summary: Lis1 is required for interkinetochore tension and checkpoint protein removal. Reason: The phenotype concerns kinetochore composition/tension downstream of dynein activity; acceptable but non-core. Supporting Evidence: PMID:16107559 Our mutant analyses show that Lis1/dynactin have at least two independent functions during mitosis: first promoting centrosome separation and bipolar spindle assembly during prophase/prometaphase, and subsequently generating interkinetochore tension and transporting checkpoint proteins off kinetochores during metaphase, thus promoting timely anaphase onset. |
| GO:0051642 centrosome localization | IMP PMID:22764052 Regulation of dynein localization and centrosome positioning... | ACCEPT | Summary: Lis-1 is required for centrosome detachment from the cortex and attachment to the nucleus in spermatocytes. Reason: Direct IMP; centrosome positioning via nuclear-envelope dynein is a conserved LIS1 function (nucleus-centrosome coupling). Supporting Evidence: PMID:22764052 We found that centrosomes do not properly detach from the cell cortex at the onset of meiosis in most Lis-1 spermatocytes; centrosomes that do break cortical associations fail to attach to the nucleus. PMID:22764052 We present a model in which Lis-1 and asun cooperate to regulate dynein localization and centrosome positioning during Drosophila spermatogenesis. |
| GO:0051647 nucleus localization | IMP PMID:10559989 Drosophila Lissencephaly-1 functions with Bic-D and dynein i... | ACCEPT | Summary: DLis-1 required for positioning of the oocyte nucleus. Reason: Core nuclear positioning function. Supporting Evidence: PMID:10559989 DLis-1 is further required for nurse-cell-to-oocyte transport during oocyte growth, and for the positioning of the nucleus in the oocyte. |
| GO:0051661 maintenance of centrosome location | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: maintenance of centrosome location. Reason: Consistent with fly data that Lis-1 is required to keep centrosomes attached to the nucleus in spermatocytes (nucleus-centrosome coupling) and with the C. elegans ortholog. Supporting Evidence: PMID:22764052 We found that centrosomes do not properly detach from the cell cortex at the onset of meiosis in most Lis-1 spermatocytes; centrosomes that do break cortical associations fail to attach to the nucleus. |
| GO:0061883 clathrin-dependent endocytosis involved in vitellogenesis | IDA PMID:26265702 Efficient Endocytic Uptake and Maturation in Drosophila Oocy... | KEEP AS NON CORE | Summary: Lis1 depletion impairs endocytic uptake and maturation of yolk in oocytes. Reason: Tissue-specific consequence of dynein regulation; non-core. Supporting Evidence: PMID:26265702 These results suggest that, in addition to Dmn, Dynein and its regulator Lis1 are required for efficient endocytosis in Drosophila oocytes. |
| GO:0070840 dynein complex binding | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule: dynein complex binding. Reason: Supported by co-immunoprecipitation of Drosophila Lis1 with dynein and dynactin, and conserved across the family. Supporting Evidence: PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits |
| GO:0070840 dynein complex binding | IPI PMID:16107559 Live imaging of Drosophila brain neuroblasts reveals a role ... | ACCEPT | Summary: Lis1 co-immunoprecipitates with dynein heavy chain. Reason: Direct experimental support for dynein complex binding, the physical basis of dynein regulation. Supporting Evidence: PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits PMID:16107559 In summary, Lis1/dynactin/dynein coimmunoprecipitate, localize to centrosome/spindle poles, and are transiently colocalized with the checkpoint protein Rod on prometaphase kinetochores before enrichment on kMTs. |
| GO:0070840 dynein complex binding | ISS PMID:10737922 Homologs of the alpha- and beta-subunits of mammalian brain ... | ACCEPT | Summary: ISS from human LIS1 (P43034): dynein complex binding. Reason: The cited paper establishes the high conservation of the Drosophila LIS1 homolog (and its inability to bind the fly PAF-AH alpha homolog), which underpins similarity-based transfer; dynein binding is independently confirmed experimentally in Drosophila (PMID:16107559). Supporting Evidence: PMID:10737922 Our study shows that the beta-subunit homolog is highly conserved from Drosophila to mammals PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits |
| GO:0072499 photoreceptor cell axon guidance | IMP PMID:21943192 New dystrophin/dystroglycan interactors control neuron behav... | KEEP AS NON CORE | Summary: Lis1 mutations cause improper photoreceptor axon path-finding. Reason: Screen-level developmental phenotype; non-core. Supporting Evidence: PMID:21943192 Our study first found that mutations in chif, CG34400, Nrk, Lis1, capt and Cam cause improper axon path-finding |
| GO:0098930 axonal transport | IMP PMID:11056531 Drosophila Lis1 is required for neuroblast proliferation, de... | ACCEPT | Summary: Lis1 is required for axonal transport in mushroom body neurons. Reason: Direct IMP evidence. Supporting Evidence: PMID:11056531 Lis1 is essential for neuroblast proliferation and axonal transport, as shown by a mosaic analysis using a Lis1 null mutation. |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000108 | ACCEPT | Summary: Inferred axon cytoplasm from retrograde axonal transport. Reason: Consistent with Lis1 acting on dynein cargo transport in axons. Supporting Evidence: PMID:28837701 In summary, our results suggest that Lis-1 has a function in GF synapse development and that both Lis1 and dynactin play a role in Nrg retrograde trafficking. |
| GO:0140659 cytoskeletal motor regulator activity | IMP PMID:23918939 Lissencephaly-1 promotes the recruitment of dynein and dynac... | NEW | Summary: Drosophila Lis1 binds and regulates cytoplasmic dynein: it promotes dynein-dynactin association and recruitment of dynein-dynactin to cargo (mRNA localization complexes, nuclear surface, spindle poles) and is required for dynein-driven processes throughout development. Reason: This is the informative MF behind the dynein complex binding annotations and matches the core MF of human LIS1 (PAFAH1B1) and the nucleokinesis module. Fly data show Lis1 physically associates with dynein/dynactin and modulates dynein-dynactin assembly and cargo recruitment; the parent regulator term is used because Lis1 can both promote and restrain dynein activity depending on context. Supporting Evidence: PMID:23918939 Furthermore, we provide evidence that Lis1 levels regulate the overall association of dynein with dynactin. PMID:23918939 Surprisingly, given its well-documented role in regulating dynein mechanochemistry, we uncovered an important requirement for Lis1 in promoting the recruitment of dynein and its accessory complex dynactin to RNA localization complexes. PMID:22764052 LIS-1 colocalizes with dynein-dynactin at the nuclear surface and spindle poles of male germ cells and is required for recruiting dynein-dynactin to these sites. PMID:16107559 Using anti-Lis1 antibodies, we could immunoprecipitate both dynein and dynactin subunits file:DROME/Lis-1/Lis-1-deep-research-falcon.md Its effect on velocity in purified assays need not mean that its physiological function is to inhibit cargo movement. |
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Download this section (compressed HTML)Q: Is the Lis1-Mad (SMAD) interaction and BMP-signalling role in ovarian germline stem cells direct and conserved, or an indirect consequence of dynein-dependent trafficking of receptor/SMAD complexes?
Suggested experts: Drosophila germline stem cell biologists, TGF-beta/BMP signalling researchers
Q: Should LIS1 orthologs carry cytoskeletal motor activator activity (GO:0140660) rather than the regulator parent GO:0140659, given fly evidence that Lis1 promotes dynein-dynactin assembly and cargo recruitment?
Suggested experts: dynein motor biophysicists, GO molecular function editors
Experiment: Test whether a dynein-binding-deficient Lis1 point mutant (e.g. at the conserved propeller-dynein interface) rescues oocyte nucleus migration, neuroblast spindle assembly and GSC maintenance, to separate dynein-dependent from putative dynein-independent (Mad-binding) functions.
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Download this section (compressed HTML)Lissencephaly-1 (Lis-1) encodes a regulator of the cytoplasmic dynein-1 motor complex, binding to Dynein heavy chain and regulating dynein force production, microtubule affinity and velocity. It is involved in the transport of many of dynein's cargoes, including mRNPs, mitochondria and nuclei. The Lis-1 product is also a non-catalytic subunit of platelet-activating factor acetylhydrolase.
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