NudF is the Aspergillus nidulans ortholog of the lissencephaly protein LIS1 (Pac1 in budding yeast), a 444-residue homodimeric regulator of cytoplasmic dynein with an N-terminal LisH/coiled-coil dimerization region and a seven-bladed WD40 beta-propeller. It acts in the dynein/dynactin pathway (with the heavy chain NudA, NudE and NudC) that distributes nuclei along the multinucleate hypha: temperature-sensitive or null nudF mutants accumulate nuclei in the conidial end of the germ tube, and dynein heavy-chain point mutations bypass the loss of NudF. NudF binds the coiled-coil domain of NudE and co-purifies with dynein. It travels as comets at microtubule plus ends near the hyphal tip (recruited by the CLIP-170 homolog ClipA and by NudE) and localizes to spindle pole bodies in mitosis, where it is needed to target dynein to the spindle poles. NudF is required to initiate dynein-driven retrograde transport of early endosomes and peroxisomes from the hyphal tip, but not for the speed of moving cargo, and acts at the step that switches dynein from its autoinhibited phi conformation to an open, activatable state. Loss of NudF also alters microtubule dynamics and impairs conidiation and sexual development.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000132 establishment of mitotic spindle orientation | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: UniRule/HAMAP family transfer of establishment of mitotic spindle orientation. Reason: Spindle orientation/positioning by cortical dynein and Pac1/LIS1 is well established in budding yeast and animal cells, and the HAMAP rule transfers it across the LIS1/nudF family. In A. nidulans the documented NudF phenotype is nuclear distribution along the hypha plus a role in targeting dynein to spindle pole bodies; spindle orientation per se has not been assayed for nudF. The family-level inference is plausible for a conserved dynein regulator but is not the characterized function in this organism, so it is kept as non-core. Supporting Evidence: file:EMENI/nudF/nudF-uniprot.txt Required for localization of dynein to the mitotic PMID:15930134 the function of NUDF is important for cytoplasmic dynein's targeting to the spindle poles |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to spindle pole. Reason: NudF localizes to mitotic spindle poles (spindle pole bodies) by live imaging; the broader spindle pole term is correct. Supporting Evidence: PMID:15930134 In Aspergillus nidulans, cytoplasmic dynein and NUDF/LIS1 are found at the spindle poles during mitosis |
| GO:0005515 protein binding | IPI PMID:10931877 The LIS1-related NUDF protein of Aspergillus nidulans intera... | REMOVE | Summary: NudF interacts with the N-terminal coiled-coil of NudE by yeast two-hybrid and co-precipitation. Reason: The NudF-NudE interaction is real and functionally important (nudE is a multicopy suppressor of nudF7), but generic protein binding carries no functional information. NudE is a dynein regulator, not a dynein subunit, so dynein complex binding would not be the right replacement for this row; the informative functions of NudF (dynein regulation, dynein complex binding) are captured elsewhere in this review. Supporting Evidence: PMID:10931877 NUDF protein interacts with the Aspergillus NUDE coiled-coil in a yeast two-hybrid system PMID:10931877 In addition, NUDF coprecipitates with an epitope-tagged NUDE. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA cytoplasm for the LIS1 family. Reason: NudF is a cytoplasmic protein found on microtubule plus ends and spindle pole bodies; the IBA is consistent with all data. Supporting Evidence: file:EMENI/nudF/nudF-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. |
| GO:0005737 cytoplasm | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule cytoplasm. Reason: Correct, if general; NudF acts in the cytoplasm on microtubules. Supporting Evidence: file:EMENI/nudF/nudF-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. |
| GO:0005816 spindle pole body | IDA PMID:15930134 Cytoplasmic dynein's mitotic spindle pole localization requi... | ACCEPT | Summary: GFP-NudF localizes to spindle pole bodies during mitosis, independently of microtubules and of dynein function. Reason: Direct localization evidence; persistence after benomyl treatment indicates SPB association rather than accumulation at microtubule minus ends. SPB-localized NudF is needed for dynein targeting to the spindle poles. Supporting Evidence: PMID:15930134 Thus, dynein and NUDF are likely to bind to the SPB rather than just accumulate at the minus ends of microtubules. PMID:15930134 although NUDF's spindle pole localization did not require the full function of dynein, the spindle pole localization of dynein is positively regulated by NUDF |
| GO:0005816 spindle pole body | IDA PMID:18390647 The nuclear migration protein NUDF/LIS1 forms a complex with... | ACCEPT | Summary: NudF colocalizes and interacts (BiFC) with NudC and BnfA at spindle pole bodies. Reason: Direct imaging evidence of NudF at SPBs, with NudC by bimolecular fluorescence complementation; the colocalizes_with qualifier is appropriate. Supporting Evidence: PMID:18390647 We showed by bimolecular fluorescence complementation microscopy that NUDC directly interacted with NUDF at SPBs at different stages of the cell cycle. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoskeleton. Reason: NudF is associated with the microtubule cytoskeleton (plus-end comets); correct but general. Supporting Evidence: PMID:11369237 Both NUDA and NUDF are located at the ends of microtubules |
| GO:0005875 microtubule associated complex | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule part_of microtubule associated complex. Reason: NudF co-purifies with dynein and dynactin and travels with them at microtubule plus ends; as a dynein-associated regulator it is part of microtubule-associated dynein complexes. Supporting Evidence: PMID:20876661 We first used mild extraction conditions (see Materials and Methods) under which regulatory proteins such as dynactin and NUDF/LIS1 co-purify with dynein |
| GO:0007017 microtubule-based process | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule microtubule-based process. Reason: Broad but correct: NudF functions in dynein-driven, microtubule-based nuclear and endosome movement. Supporting Evidence: PMID:9236777 our data suggests that NUDF affects nuclear migration by acting on the dynein motor system |
| GO:0007097 nuclear migration | IMP PMID:10931877 The LIS1-related NUDF protein of Aspergillus nidulans intera... | ACCEPT | Summary: nudF7 mutant nuclear distribution defect, suppressed by multicopy nudE. Reason: NudF was identified in a screen for nuclear distribution (nud) mutants; loss of function blocks migration of nuclei into the growing hypha. Genetic suppression by dynein heavy chain alleles places NudF in the dynein pathway, so this is a core process. The more specific child GO:0030473 nuclear migration along microtubule is used in core_functions. Supporting Evidence: PMID:10931877 Multicopy plasmids with the nudE gene improve the growth, conidiation and nuclear distribution of the nudF7 mutant PMID:10931877 The nudF gene of the filamentous fungus Aspergillus nidulans acts in the cytoplasmic dynein/dynactin pathway and is required for distribution of nuclei. |
| GO:0007097 nuclear migration | IMP PMID:7612965 NudF, a nuclear migration gene in Aspergillus nidulans, is s... | ACCEPT | Summary: Cloning of nudF by complementation of a temperature-sensitive nuclear migration mutant. Reason: NudF was identified in a screen for nuclear distribution (nud) mutants; loss of function blocks migration of nuclei into the growing hypha. Genetic suppression by dynein heavy chain alleles places NudF in the dynein pathway, so this is a core process. The more specific child GO:0030473 nuclear migration along microtubule is used in core_functions. Supporting Evidence: PMID:7612965 we cloned a gene, nudF, which is required for nuclear migration during vegetative growth as well as development |
| GO:0008017 microtubule binding | IDA PMID:11369237 The Aspergillus cytoplasmic dynein heavy chain and NUDF loca... | KEEP AS NON CORE | Summary: GFP-NudF localizes to dynamic microtubule ends; nudF mutants alter microtubule dynamics. Reason: The cached record is abstract-only; the abstract reports localization of NudF at microtubule ends and effects on microtubule dynamics, not a biochemical microtubule-binding assay. The curator read the full text, and microtubule association is conserved in the LIS1 family (human LIS1 carries this term), so the annotation is retained; but NudF's plus-end localization depends on ClipA and NudE (PMID:16467375) and its main biochemical partner is dynein, so microtubule binding is not treated as core. Supporting Evidence: PMID:11369237 Both NUDA and NUDF are located at the ends of microtubules PMID:16467375 we suggest that CLIPA and NUDE both recruit NUDF to the microtubule plus end |
| GO:0015630 microtubule cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA microtubule cytoskeleton (NudF itself and Pac1 among the donors). Reason: NudF acts on microtubule plus ends and spindle pole bodies; the IBA is correct. NudF's own experimental data are among the node's sources, as expected. Supporting Evidence: PMID:11369237 Both NUDA and NUDF are located at the ends of microtubules |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA microtubule cytoskeleton. Reason: Consistent with the IBA and with localization data. Supporting Evidence: PMID:11369237 Both NUDA and NUDF are located at the ends of microtubules |
| GO:0043935 sexual sporulation resulting in formation of a cellular spore | IMP PMID:7612965 NudF, a nuclear migration gene in Aspergillus nidulans, is s... | KEEP AS NON CORE | Summary: nudF mutants are defective in sexual development. Reason: nudF loss impairs development as well as vegetative growth. In A. nidulans these defects follow from the failure to distribute nuclei into developing structures, so they are downstream consequences of the core dynein-regulatory function rather than a distinct role; kept as non-core. The acts_upstream_of_or_within qualifier appropriately reflects this. Supporting Evidence: PMID:7612965 required for nuclear migration during vegetative growth as well as development |
| GO:0048315 conidium formation | IMP PMID:7612965 NudF, a nuclear migration gene in Aspergillus nidulans, is s... | KEEP AS NON CORE | Summary: nudF mutants are defective in conidiation. Reason: nudF loss impairs development as well as vegetative growth. In A. nidulans these defects follow from the failure to distribute nuclei into developing structures, so they are downstream consequences of the core dynein-regulatory function rather than a distinct role; kept as non-core. The acts_upstream_of_or_within qualifier appropriately reflects this. Supporting Evidence: PMID:7612965 required for nuclear migration during vegetative growth as well as development PMID:10931877 Multicopy plasmids with the nudE gene improve the growth, conidiation and nuclear distribution of the nudF7 mutant |
| GO:0051012 microtubule sliding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: UniRule microtubule sliding. Reason: The UniProt function text states only that NudF 'may enhance dynein-mediated microtubule sliding'; this is a family-level hypothesis derived from cortical dynein in yeast, and there is no A. nidulans assay of microtubule sliding. As a dynein regulator NudF could contribute to any dynein-driven sliding, so the row is not removed, but it is not a characterized function (consistent with the human LIS1 review). Supporting Evidence: file:EMENI/nudF/nudF-uniprot.txt May enhance dynein-mediated microtubule sliding by targeting dynein |
| GO:0070840 dynein complex binding | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule dynein complex binding. Reason: NudF co-purifies with dynein, dynein heavy-chain mutations bypass nudF loss, and NudF controls the conformation of the dynein motor; direct dynein binding by LIS1 is conserved (human LIS1 binds the dynein motor domain). Core molecular function. Supporting Evidence: PMID:20876661 regulatory proteins such as dynactin and NUDF/LIS1 co-purify with dynein PMID:9236777 The snfC mutations are bypass suppressors of nudF and genetic evidence indicated that NUDA and NUDF act in the same nuclear migration pathway. |
| GO:0140659 cytoskeletal motor regulator activity | IMP PMID:31562232 LIS1 regulates cargo-adapter-mediated activation of dynein b... | NEW | Summary: NudF is required for cargo-adapter (HookA)-mediated activation of dynein in vivo and acts by relieving dynein autoinhibition. Reason: The best-supported molecular function of NudF is regulation of the dynein motor: NudF is required for dynein activation by the adapter DeltaC-HookA, and dynein mutations that prevent the autoinhibited phi conformation bypass the need for NudF. Consistent with the module and the human LIS1 review (GO:0140659). Not currently in GOA for nudF. Supporting Evidence: PMID:31562232 Together, these results indicate that NudF/LIS1 is critically required for ΞC-HookAβmediated dynein activation in A. PMID:31562232 Our results suggest a novel mechanism of LIS1 action that promotes the switch of dynein from the autoinhibited state to an open state to facilitate dynein activation. PMID:34428469 Importantly, the wB-AAA3 mutation suppressed the colony growth defect of the ΞnudF mutant, suggesting that the wB-AAA3 mutation allows the function of NudF/LIS1 to be bypassed |
| GO:0072382 minus-end-directed vesicle transport along microtubule | IMP PMID:22711696 Lis1 is an initiation factor for dynein-driven organelle tra... | NEW | Summary: Lis1/NudF deletion causes early endosomes and peroxisomes to accumulate at hyphal tips because dynein-driven retrograde runs are rarely initiated. Reason: Participation test: NudF is a dynein regulator that acts on the motor at the initiation step of each retrograde run (it is not a cargo or a substrate), the same role in which LIS1 is annotated to retrograde axonal transport. Comparator: human PAFAH1B1 and NDEL1 carry dynein-driven transport processes in their reviews. Evidence is from deletion mutants in A. nidulans in two laboratories. Supporting Evidence: PMID:22711696 In the absence of Lis1, endosomes and peroxisomes accumulate at hyphal tips, and retrograde movements are quite rare PMID:22711696 Based on these observations, we propose that Lis1 has a general role in initiating dynein-driven motility. PMID:22711696 Moreover, Lis1, unlike dynein and dynactin, was absent from moving dynein cargos |
| GO:0035371 microtubule plus-end | IDA PMID:12686603 Accumulation of cytoplasmic dynein and dynactin at microtubu... | NEW | Summary: GFP-NudF forms comet-like structures at microtubule plus ends near the hyphal tip. Reason: Plus-end localization of NudF is documented by live imaging in several studies and is where NudF, dynein and dynactin accumulate before minus-end-directed runs; the parent cytoskeleton terms in GOA do not capture it. Supporting Evidence: PMID:12686603 In the filamentous fungus Aspergillus nidulans, both cytoplasmic dynein and NUDF, the homolog of the LIS1 protein, localize to microtubule plus ends as comet-like structures. |
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Download this section (compressed HTML)Q: Is NudF's role at spindle pole bodies (targeting dynein and recruiting NudC/BnfA) separable from its role in initiating dynein runs from microtubule plus ends, and does it contribute to spindle orientation in hyphae?
Suggested experts: Aspergillus cell biologists, dynein regulation specialists
Experiment: Separation-of-function nudF alleles defective in dynein motor-domain binding versus NudE binding, scored for nuclear distribution, early endosome transport and SPB dynein recruitment.
Hypothesis: Motor-domain binding by NudF is required for all dynein functions, whereas NudE binding is dispensable when NudF is abundant.
Type: genetics with live imaging
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