Bicaudal-D (BicD) is a dimeric coiled-coil protein of the BICD family that acts as an activating cargo adaptor for cytoplasmic dynein-1. Its N-terminal coiled coils bind dynein and dynactin, while its C-terminal cargo-binding domain binds the RNA-binding protein Egalitarian (Egl), GTP-bound Rab GTPases (Rab6, Rab2, Rab30, Rab39) and clathrin heavy chain. BicD is autoinhibited until cargo binds; Egl bound to an RNA localization signal licenses BicD to recruit dynein-dynactin and switch on long-distance minus-end-directed transport, making Egl-BicD the minimal link between localizing mRNAs and the motor. In the germline, BicD-dynein transports determinant mRNAs and proteins from nurse cells into the pro-oocyte and is required for oocyte specification, oocyte microtubule polarity and localization of oskar, bicoid and gurken mRNAs; dominant alleles mislocalize the posterior determinant nanos and produce bicaudal (double-abdomen) embryos. BicD also localizes mRNAs apically in blastoderm embryos and neuroblasts (e.g. inscuteable), is required for apical migration of photoreceptor precursor nuclei, supports synaptic vesicle recycling at the neuromuscular junction by promoting clathrin transport, and, redundantly with its paralog BicDR, transports Rab6 and Spindle-F vesicles in growing bristle shafts. In the oocyte BicD is also required for the biogenesis of annulate lamellae, cytoplasmic stacks of nuclear pore complexes; BicD knockdown leaves Nup358 soluble instead of condensed into the granules from which annulate lamellae assemble.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003729 mRNA binding | NAS NOT PMID:12446149 Intracellular mRNA localization: motors move messages. | ACCEPT | Summary: NOT mRNA binding (NAS, from a review of motor-driven mRNA transport). BicD is recruited to localizing transcripts through the RNA-binding protein Egalitarian rather than by binding RNA itself. Reason: The negated statement is consistent with the biochemistry: Egl, not BicD, directly recognizes mRNA localization signals, and BicD associates with RNA through its C-terminal cargo-binding domain contacting Egl. Reconstitution shows RNA promotes the Egl-BicD interaction rather than binding BicD directly. The review cited is abstract-only here, but the negation is well supported by later primary work. Supporting Evidence: PMID:19515976 despite lacking a canonical RNA-binding motif, Egl directly recognizes active localization elements PMID:19515976 We also reveal a physical interaction between Egl and a conserved domain for cargo recruitment in BicD PMID:29944118 A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin file:DROME/BicD/BicD-deep-research-falcon.md BicD should not itself be annotated as the principal sequence-specific RNA-binding protein; it is the motor adaptor downstream of Egl |
| GO:0005515 protein binding | IPI PMID:17329360 Rab6 mediates membrane organization and determinant localiza... | MODIFY | Summary: Protein binding (IPI) with Rab6 from Coutelis and Ephrussi 2007: Rab6 is found in a complex with BicD in vivo. Reason: Generic protein binding is uninformative. The partner is the small GTPase Rab6, a membrane cargo-recruiting partner that binds the BicD C-terminal domain (UniProt region 699-722). The informative term is small GTPase binding, which is also supported by GTP-dependent Rab6/Rab2/Rab30/Rab39 binding in affinity-chromatography studies. Proposed replacements: small GTPase binding Supporting Evidence: PMID:17329360 We show that, in vivo, Rab6 is found in a complex with Bicaudal-D, and that Rab6 and Bicaudal-D cooperate in oskar mRNA localization PMID:25453831 Rab30 interactors from the detergent lysate included the dynein adaptor BicD (that also binds Rab6 and Rab2) file:DROME/BicD/BicD-uniprot.txt oogenesis, plays a specific role, together with Rab6 but independently |
| GO:0005515 protein binding | IPI PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | MODIFY | Summary: Protein binding (IPI) with clathrin heavy chain (Chc), the most abundant BicD co-precipitating protein from head extracts; binding is direct. Reason: Generic protein binding is uninformative. The paper shows direct binding of the BicD C-terminal domain to clathrin heavy chain, and this is already captured by the separate clathrin heavy chain binding IPI row from the same paper; that is the appropriate informative replacement. Proposed replacements: clathrin heavy chain binding Supporting Evidence: PMID:20111007 BicD binds Chc directly and interacts genetically with components of the pathway for clathrin-mediated membrane trafficking |
| GO:0005737 cytoplasm | IDA PMID:2590944 Structure of the Drosophila BicaudalD protein and its role i... | ACCEPT | Summary: Cytoplasm (IDA): BicD protein is distributed in the oocyte cytoplasm. Reason: BicD is a soluble coiled-coil adaptor of cytoplasmic dynein; immunolocalization shows cytoplasmic distribution in oocytes, where it concentrates with localized determinants. Supporting Evidence: PMID:2590944 BicD protein is uniformly distributed throughout wild-type oocytes |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | ACCEPT | Summary: Golgi apparatus (IBA) from the BICD family node, seeded by human BICD2/BICD1 and mouse Bicd2. Reason: The Golgi association of BICD proteins derives from their binding to Golgi Rab GTPases. Drosophila BicD is a GTP-dependent effector of Rab6, Rab2, Rab30 and Rab39 and was identified as a Golgi-localized coiled-coil protein among Rab30 effectors, so it lies within the clade that inherited this location; is_active_in is appropriate for the Rab-bound membrane pool. Supporting Evidence: PMID:19001129 two further Golgi-localized coiled-coil proteins, BicaudalD (BicD) and dp115 PMID:25453831 Rab30 interactors from the detergent lysate included the dynein adaptor BicD (that also binds Rab6 and Rab2) |
| GO:0005829 cytosol | HDA PMID:25294944 Subcellular localisations of the CPTI collection of YFP-tagg... | ACCEPT | Summary: Cytosol (HDA) from the CPTI YFP-trap localization survey in embryos. Reason: BicD lacks transmembrane or organelle-targeting sequences and its autoinhibited, cargo-free pool is soluble; a cytosolic localization in a high-throughput embryo screen is consistent with this. BicD is not named in the cached main text (likely in supplementary data), so this acceptance defers to the curator. Supporting Evidence: PMID:2590944 BicD protein is uniformly distributed throughout wild-type oocytes |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol (IBA) from the BICD family node. Reason: The soluble autoinhibited adaptor pool is cytosolic; cargo binding recruits BicD to dynein-dynactin on microtubules. Consistent with the human BICD2 review. Supporting Evidence: PMID:32378283 The dynein adaptor Drosophila Bicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoskeleton (IEA from UniProt subcellular location, which is itself ECO:0000305 inference). Reason: BicD is not a structural cytoskeletal polymer (the early intermediate-filament-like model was not borne out), but it functions bound to dynein-dynactin on microtubules; the broad location is acceptable as in the human BICD2 review. Supporting Evidence: PMID:38264934 In the dynein-dynactin-Bicaudal-D transport machinery, Bicaudal-D (BicD) links the cargo to the motor |
| GO:0007293 germarium-derived egg chamber formation | IMP PMID:11254350 Bicaudal-D is essential for egg chamber formation and cytosk... | KEEP AS NON CORE | Summary: Germarium-derived egg chamber formation (IMP) from heptad-repeat deletion alleles of BicD. Reason: The phenotype is real and specific to the BicD germline requirement, but it is a developmental consequence of loss of dynein-dependent transport into the oocyte rather than a direct function; keep as non-core developmental process. Supporting Evidence: PMID:11254350 In the germarium Bic-D is required for the organization of the egg chamber and the structural integrity of the oocyte and nurse cells |
| GO:0007294 germarium-derived oocyte fate determination | IMP PMID:1959135 Requirement for phosphorylation and localization of the Bica... | KEEP AS NON CORE | Summary: Germarium-derived oocyte fate determination (IMP), the classic early BicD requirement. Reason: BicD is required for oocyte differentiation because the Egl-BicD-dynein machinery transports determinant mRNAs and proteins into the pro-oocyte. This is a well-established and important developmental role, but it is a downstream outcome of the adaptor function; kept as non-core in the sense used in this project (developmental process). Supporting Evidence: PMID:1959135 Bic-D is required for the differentiation of an oocyte and hence for fertility PMID:1959135 Recessive mutations in Bic-D block the oocyte-specific accumulation of its own and other RNAs |
| GO:0007309 oocyte axis specification | TAS PMID:11784091 Structure and function of the egg cortex from oogenesis thro... | KEEP AS NON CORE | Summary: Oocyte axis specification (TAS) from a review of the egg cortex. Reason: BicD mutants mislocalize posterior (oskar/nanos) and anterior determinants and dominant alleles produce double-abdomen embryos, so participation in establishing oocyte axes via mRNA localization is well supported by primary literature, although the cited review is abstract-only here and does not mention BicD in its abstract. Developmental outcome; non-core. Supporting Evidence: PMID:2590944 it encodes a coiled-coil protein similar to the carboxy-terminal portion of the myosin heavy chain PMID:8951073 we show that Bic-D is required for the localization of specific mRNAs at both the anterior and posterior of the oocyte PMID:17329360 We show that, in vivo, Rab6 is found in a complex with Bicaudal-D, and that Rab6 and Bicaudal-D cooperate in oskar mRNA localization |
| GO:0007312 oocyte nucleus migration involved in oocyte dorsal/ventral axis specification | TAS PMID:9642168 Control of mRNA stability and translation during Drosophila ... | UNDECIDED | Summary: Oocyte nucleus migration involved in D/V axis specification (TAS) from a review on mRNA stability and translation control. Reason: The cited review is abstract-only and its abstract concerns translational control and mRNA stability, not nuclear migration. The same review supports an identical TAS on egl. Direct primary evidence that BicD drives migration of the oocyte nucleus was not found in the accessible literature; Bic-D::GFP accumulates next to the oocyte nucleus and a role in tethering the nucleus was only proposed. Dynein and Lis-1 are required for oocyte nucleus positioning, so a BicD role is plausible but unverified here. Supporting Evidence: PMID:10825285 Asymmetric subcellular accumulation of Bic-D and the polarization of the oocyte nucleus may reflect the function of this localization machinery in vectorial mRNA localization and in tethering of the oocyte nucleus |
| GO:0008093 cytoskeletal adaptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Cytoskeletal adaptor activity (IEA, InterPro BICD family). Reason: Core molecular function. BicD links cargoes (Egl-bound mRNAs, Rab6-positive membranes, clathrin) to the dynein-dynactin motor. Reconstitution with purified Drosophila proteins shows BicD and Egl are sufficient to link mRNA to dynein-dynactin for long-distance transport. Supporting Evidence: PMID:38264934 In the dynein-dynactin-Bicaudal-D transport machinery, Bicaudal-D (BicD) links the cargo to the motor PMID:29944118 A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin PMID:19515976 We also reveal a physical interaction between Egl and a conserved domain for cargo recruitment in BicD |
| GO:0008103 oocyte microtubule cytoskeleton polarization | IMP PMID:11254350 Bicaudal-D is essential for egg chamber formation and cytosk... | KEEP AS NON CORE | Summary: Oocyte microtubule cytoskeleton polarization (IMP). Reason: BicD mutant ovaries fail to establish and maintain the polarized oocyte microtubule network. This is likely an indirect consequence of failed dynein-dependent transport (e.g. of Rab6-dependent membranes and determinants) rather than a direct microtubule-organizing activity; retain as non-core. Supporting Evidence: PMID:11254350 Bic-D function is required for both the establishment of the polarized microtubule network and its maintenance throughout oogenesis PMID:17329360 We show that, in vivo, Rab6 is found in a complex with Bicaudal-D, and that Rab6 and Bicaudal-D cooperate in oskar mRNA localization |
| GO:0008298 intracellular mRNA localization | IMP PMID:15530398 Inscuteable mRNA localization is dynein-dependent and regula... | ACCEPT | Summary: Intracellular mRNA localization (IMP): Egl/BicD/dynein mediates apical localization of inscuteable mRNA in neuroblasts. Reason: Localization of specific mRNAs by dynein is the best-characterized BicD process, established in oocytes, blastoderm embryos and neuroblasts. BicD performs the linking/activation step of this transport. Supporting Evidence: PMID:15530398 the Egalitarian (Egl)/Bicaudal-D (BicD)/dynein mRNA transport machinery mediates apical localization of insc mRNA transcripts in neuroblasts PMID:8951073 we show that Bic-D is required for the localization of specific mRNAs at both the anterior and posterior of the oocyte PMID:29944118 A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin |
| GO:0022416 chaeta development | IGI PMID:38264934 Role of BicDR in bristle shaft construction and support of B... | KEEP AS NON CORE | Summary: Chaeta development (IGI with BicDR). Reason: BicD and its paralog BicDR act redundantly in bristle shaft construction, where they support dynein-dependent transport of Rab6 and Spn-F towards the bristle tip. A genuine but downstream developmental role. Supporting Evidence: PMID:38264934 Here we showed that the reduced activity of BicD and BicDR affects the Rab6 and Spn-F levels and localization in the growing bristle, linking BicD and BicDR to the dynein-dependent microtubule transport of vesicles and bristle factors to their proper position in the bristle where they perform their function PMID:38264934 Together with BicD, it contributes to the organization and stability of the actin cytoskeleton in the not-yet-chitinized bristle shaft file:DROME/BicD/BicD-uniprot.txt Functions redundantly with BicDR |
| GO:0030100 regulation of endocytosis | IMP PMID:24718986 Clathrin heavy chain plays multiple roles in polarizing the ... | KEEP AS NON CORE | Summary: Regulation of endocytosis (IMP) from Chc/BicD work in oocytes. Reason: Bic-D is needed for elevated endocytic activity at the posterior of the oocyte, partly indirectly through oskar mRNA localization and partly through transport of Chc mRNA and protein to the oocyte cortex. The effect is real but indirect (transport of endocytic machinery), so non-core. Supporting Evidence: PMID:24718986 our results show that Bic-D is also needed for the elevated endocytic activity at the posterior of the oocyte PMID:24718986 Apart from affecting endocytosis indirectly by its role in osk mRNA localization |
| GO:0030669 clathrin-coated endocytic vesicle membrane | IDA PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | KEEP AS NON CORE | Summary: Colocalizes with clathrin-coated endocytic vesicle membrane (IDA): BicD::eGFP puncta overlap with Chc puncta in presynaptic boutons. Reason: The colocalizes_with qualifier correctly limits the claim. Most intracellular Chc puncta in boutons overlap BicD puncta, consistent with BicD transporting clathrin-associated material, but the puncta were not shown to be endocytic vesicles and BicD is a transient peripheral adaptor. Retain as non-core. Supporting Evidence: PMID:20111007 puncta within the bouton cytoplasm and 70% of these ( n =46) co-localised with a discernible punctum of BicD |
| GO:0031267 small GTPase binding | IPI PMID:19001129 Golgi coiled-coil proteins contain multiple binding sites fo... | ACCEPT | Summary: Small GTPase binding (IPI) with Rab30. Reason: BicD was recovered as an abundant Rab30 effector and the interaction confirmed with a specific antibody; BicD is an established Rab GTPase effector (Rab6, Rab2, Rab30, Rab39), and Rab binding is how it engages membrane cargo. Supporting Evidence: PMID:19001129 the interaction between Rab30 and BicD was confirmed using a specific antibody PMID:25453831 BicD also showed GTP-dependent binding to Rab30 and to the Rab2 relative Rab39 |
| GO:0031267 small GTPase binding | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | ACCEPT | Summary: Small GTPase binding (IPI) from a comprehensive affinity-chromatography map of Drosophila Rab effectors. Reason: BicD bound GTP-locked Rab6, Rab2, Rab30 and Rab39 in a GTP-dependent manner, the behaviour of a genuine Rab effector. Rab binding via the C-terminal cargo-binding domain is how BicD recruits membrane cargo to dynein. Supporting Evidence: PMID:25453831 Rab30 interactors from the detergent lysate included the dynein adaptor BicD (that also binds Rab6 and Rab2) PMID:25453831 BicD also showed GTP-dependent binding to Rab30 and to the Rab2 relative Rab39 |
| GO:0031267 small GTPase binding | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | ACCEPT | Summary: Small GTPase binding (IPI) from a comprehensive affinity-chromatography map of Drosophila Rab effectors. Reason: BicD bound GTP-locked Rab6, Rab2, Rab30 and Rab39 in a GTP-dependent manner, the behaviour of a genuine Rab effector. Rab binding via the C-terminal cargo-binding domain is how BicD recruits membrane cargo to dynein. Supporting Evidence: PMID:25453831 Rab30 interactors from the detergent lysate included the dynein adaptor BicD (that also binds Rab6 and Rab2) PMID:25453831 BicD also showed GTP-dependent binding to Rab30 and to the Rab2 relative Rab39 |
| GO:0031267 small GTPase binding | IPI PMID:25453831 Toward a comprehensive map of the effectors of rab GTPases. | ACCEPT | Summary: Small GTPase binding (IPI) from a comprehensive affinity-chromatography map of Drosophila Rab effectors. Reason: BicD bound GTP-locked Rab6, Rab2, Rab30 and Rab39 in a GTP-dependent manner, the behaviour of a genuine Rab effector. Rab binding via the C-terminal cargo-binding domain is how BicD recruits membrane cargo to dynein. Supporting Evidence: PMID:25453831 Rab30 interactors from the detergent lysate included the dynein adaptor BicD (that also binds Rab6 and Rab2) PMID:25453831 BicD also showed GTP-dependent binding to Rab30 and to the Rab2 relative Rab39 |
| GO:0032050 clathrin heavy chain binding | IPI PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | ACCEPT | Summary: Clathrin heavy chain binding (IPI): Chc is the most abundant BicD partner in head extracts and binds BicD directly. Reason: Direct binding of Chc to the BicD C-terminal domain is shown in the paper; this is a specific cargo interaction that promotes Chc transport at synapses. Supporting Evidence: PMID:20111007 BicD binds Chc directly and interacts genetically with components of the pathway for clathrin-mediated membrane trafficking PMID:20111007 Directed transport and subcellular localisation of Chc is strongly perturbed in BicD mutant presynaptic boutons |
| GO:0034452 dynactin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynactin binding (IBA). Reason: BicD N-terminal coiled coils bind dynein and dynactin; for Drosophila BicD this is shown by in vitro binding and by reconstitution, where cargo-activated BicD recruits dynein and dynactin. Consistent with the PAINT node placement across the BICD family. Supporting Evidence: PMID:38264934 it has been shown that BicD and BicDR require it for the efficient binding to dynein and dynactin in vitro PMID:29944118 which licenses the latter protein to recruit dynein and dynactin |
| GO:0048477 oogenesis | HMP PMID:1783295 Female sterile mutations on the second chromosome of Drosoph... | KEEP AS NON CORE | Summary: Oogenesis (HMP) from a large female-sterile mutagenesis screen. Reason: BicD is essential for oogenesis (oocyte differentiation, determinant transport). The cached screen paper is abstract-only and does not name BicD in its abstract, but the requirement is well established. Broad developmental process; non-core. Supporting Evidence: PMID:1959135 Bic-D is required for the differentiation of an oocyte and hence for fertility |
| GO:0048477 oogenesis | IMP PMID:23450845 A mosaic genetic screen for genes involved in the early step... | KEEP AS NON CORE | Summary: Oogenesis (IMP) from a mosaic screen that recovered two new null alleles of BicD. Reason: Loss of BicD blocks oocyte specification in egg chambers; correct but a broad developmental outcome of the transport function. Supporting Evidence: PMID:23450845 This result showed that we were able to generate and identify two alleles of Bicaudal-D, which validated our screening strategy PMID:23450845 Egg chambers mutant for null alleles Bicaudal-D, which is on chromosome 2L, show an identical phenotype |
| GO:0048488 synaptic vesicle endocytosis | IGI PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | MODIFY | Summary: Synaptic vesicle endocytosis (IGI with endophilin A). Reason: The paper explicitly concludes that BicD is not directly required for clathrin-mediated budding or uncoating, and that BicD/dynein have a kinetic role in recycling pre-internalised membrane to the releasable pool; the EndoA interaction suppresses recycling defects. Synaptic vesicle recycling describes the supported process more accurately than the endocytic step itself. Proposed replacements: synaptic vesicle recycling Supporting Evidence: PMID:20111007 These data indicate that, even during high-frequency stimulation, BicD is not directly required for budding of clathrin-mediated vesicles from the plasma membrane or subsequent uncoating PMID:20111007 Collectively, our data indicate that BicD has a kinetic function in stimulating the rate of recycling of pre-internalised vesicles, as opposed to an obligatory role in any one step PMID:20111007 A kinetic role of BicD-mediated transport in vesicle recycling was also supported by our observation that dye release defects of BicD mutants could be fully suppressed by presynaptic overexpression of EndoA |
| GO:0050658 RNA transport | IMP PMID:17442699 A Dynein-dependent shortcut rapidly delivers axis determinat... | MODIFY | Summary: RNA transport (IMP): gurken RNA requires BicD and dynein for transport toward the ring canals. Reason: Correct but the cargo is mRNA (gurken, and by implication bicoid and oskar); mRNA transport, already annotated from other papers, is the more precise term. Proposed replacements: mRNA transport Supporting Evidence: PMID:17442699 gurken transcripts, but not control transcripts, recruit the cytoplasmic Dynein-associated co-factors Bicaudal D (BicD) and Egalitarian in the nurse cells PMID:17442699 gurken RNA requires BicD and Dynein for its transport towards the ring canals |
| GO:0051028 mRNA transport | IDA PMID:16009136 Dynein anchors its mRNA cargo after apical transport in the ... | ACCEPT | Summary: mRNA transport (IDA) from live imaging of apical mRNA transport and anchoring in blastoderm embryos. Reason: BicD is recruited with Egl and dynein to apically transported transcripts; the cached abstract focuses on dynein as an anchor, but the full-text-based IDA is consistent with the well-established BicD role in dynein-mediated mRNA transport in the embryo. Supporting Evidence: PMID:16009136 apical anchoring of RNA requires microtubules and involves dynein as a static anchor that remains with the cargo at its final destination PMID:16860745 We show that these proteins, together with the dynein motor, are recruited differentially to different RNA signals |
| GO:0051028 mRNA transport | IMP PMID:16860745 Guidance of bidirectional motor complexes by mRNA cargoes th... | ACCEPT | Summary: mRNA transport (IMP): minus-end-directed runs of localizing mRNAs depend on Egl and BicD dosage. Reason: Core process. BicD, with Egl, is recruited by RNA localization signals and increases the number and activity of dynein motors on the RNA, biasing bidirectional transport towards minus ends. Supporting Evidence: PMID:16860745 Increased minus-end motility is dependent on the dosage of RNA elements and the proteins Egalitarian (Egl) and Bicaudal-D (BicD) PMID:16860745 We show that these proteins, together with the dynein motor, are recruited differentially to different RNA signals |
| GO:0070507 regulation of microtubule cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Regulation of microtubule cytoskeleton organization (IBA). Reason: Loss of BicD disrupts oocyte microtubule polarity in Drosophila and centrosomal microtubule arrays in mammals, but these are indirect consequences of dynein-dependent transport rather than a direct regulatory activity on microtubules. Consistent with the human BICD2 review. Supporting Evidence: PMID:11254350 Bic-D function is required for both the establishment of the polarized microtubule network and its maintenance throughout oogenesis |
| GO:0070840 dynein complex binding | IBA GO_REF:0000033 | ACCEPT | Summary: Dynein complex binding (IBA). Reason: Drosophila BicD binds cytoplasmic dynein via its N-terminal coiled coil, and after cargo binding recruits dynein-dynactin in reconstitution assays. Core interaction underlying its adaptor function. Supporting Evidence: PMID:38264934 it has been shown that BicD and BicDR require it for the efficient binding to dynein and dynactin in vitro PMID:29944118 which licenses the latter protein to recruit dynein and dynactin PMID:32378283 The dynein adaptor Drosophila Bicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound |
| GO:0070840 dynein complex binding | IEA GO_REF:0000002 | ACCEPT | Summary: Dynein complex binding (IEA, InterPro BICD). Reason: As for the IBA row: dynein binding is conserved across the BICD family and shown for Drosophila BicD. Supporting Evidence: PMID:29944118 which licenses the latter protein to recruit dynein and dynactin |
| GO:0072393 microtubule anchoring at microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Microtubule anchoring at microtubule organizing center (IBA). Reason: The family-level evidence (BICD/dynein and GSK-3beta in mammalian cells) indicates an indirect role, likely through dynein transport of centrosomal anchoring proteins. No Drosophila-specific evidence contradicts inheritance, but the role is peripheral. Consistent with the human BICD2 review. Supporting Evidence: PMID:11254350 Bic-D function is required for both the establishment of the polarized microtubule network and its maintenance throughout oogenesis |
| GO:0098793 presynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Presynapse (IEA inferred from the synaptic vesicle endocytosis annotation). Reason: BicD::eGFP is present in presynaptic boutons of the larval NMJ where it colocalizes with clathrin puncta, so the location is supported, but it is one of many sites of BicD action. Supporting Evidence: PMID:20111007 puncta within the bouton cytoplasm and 70% of these ( n =46) co-localised with a discernible punctum of BicD PMID:20111007 Directed transport and subcellular localisation of Chc is strongly perturbed in BicD mutant presynaptic boutons |
| GO:0098840 protein transport along microtubule | IMP PMID:38264934 Role of BicDR in bristle shaft construction and support of B... | ACCEPT | Summary: Protein transport along microtubule (IMP) from bristle-shaft transport of Rab6 and Spn-F. Reason: BicD (with BicDR) is required for dynein-dependent transport of Rab6 and Spn-F along the microtubules of the growing bristle shaft; together with BicD-promoted Chc transport at synapses, this supports BicD acting in microtubule-based transport of protein cargo. Supporting Evidence: PMID:38264934 Here we showed that the reduced activity of BicD and BicDR affects the Rab6 and Spn-F levels and localization in the growing bristle, linking BicD and BicDR to the dynein-dependent microtubule transport of vesicles and bristle factors to their proper position in the bristle where they perform their function PMID:20111007 Directed transport and subcellular localisation of Chc is strongly perturbed in BicD mutant presynaptic boutons |
| GO:0140312 cargo adaptor activity | IMP PMID:38264934 Role of BicDR in bristle shaft construction and support of B... | MODIFY | Summary: Cargo adaptor activity (IMP) from the BicD/BicDR bristle study. Reason: GO:0140312 is defined as binding the structural scaffold of a vesicle coat (clathrin, COPII) and bridging membrane, cargo receptor and deformation machinery, i.e. a coat adaptor such as AP-2. BicD is a motor adaptor linking cargo to dynein-dynactin; the paper describes exactly this. The correct term is cytoskeletal adaptor activity. Proposed replacements: cytoskeletal adaptor activity Supporting Evidence: PMID:38264934 In the dynein-dynactin-Bicaudal-D transport machinery, Bicaudal-D (BicD) links the cargo to the motor |
| GO:2000302 positive regulation of synaptic vesicle exocytosis | IMP PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | KEEP AS NON CORE | Summary: Positive regulation of synaptic vesicle exocytosis (IMP) from FM1-43 and EJP assays at the larval NMJ. Reason: BicD mutants fail to sustain neurotransmission during high-frequency stimulation and retain pre-internalised dye, but the authors attribute this to slower recycling of internalised membrane to the releasable pool rather than to a role in the exocytic event, and state there is no obligatory requirement for BicD in exocytosis. The regulation annotation reflects the phenotypic readout; retained as non-core since synaptic vesicle recycling is the more accurate description. Supporting Evidence: PMID:20111007 Collectively, these observations provide further evidence that there is not an obligatory requirement for BicD in endocytosis or exocytosis PMID:20111007 shows that BicD/dynein transport functions in the pathway for recycling the readily releasable pool |
| GO:2000370 positive regulation of clathrin-dependent endocytosis | IMP PMID:20111007 Bicaudal-D binds clathrin heavy chain to promote its transpo... | KEEP AS NON CORE | Summary: Positive regulation of clathrin-dependent endocytosis (IMP). Reason: Reducing BicD dosage enhances the shibire (dynamin) phenotype and BicD mutants take up less membrane during intense stimulation, indicating BicD promotes a dynamin-dependent process; mechanistically this is thought to occur by transporting Chc to replenish plasma-membrane clathrin, not by participating in vesicle budding. Non-core. Supporting Evidence: PMID:20111007 The enhancement of the shi phenotype on lowering BicD dosage indicates that BicD normally promotes a dynamin-dependent process involved in neurotransmission PMID:20111007 These data indicate that, even during high-frequency stimulation, BicD is not directly required for budding of clathrin-mediated vesicles from the plasma membrane or subsequent uncoating PMID:20111007 Thus, BicD is required to augment the rate of recycling of internalised membrane |
| GO:0140660 cytoskeletal motor activator activity | IDA PMID:29944118 RNA-directed activation of cytoplasmic dynein-1 in reconstit... | NEW | Summary: Drosophila BicD, in complex with Egl and a localizing RNA, activates processive minus-end motility of dynein-dynactin in reconstitution with purified proteins. Reason: BicD is an activating dynein adaptor: purified Egl/DmBicD with dynactin increases the number of processive dynein runs in an RNA-dependent manner, and BicD is autoinhibited until cargo binds. Binding and increasing the activity of the motor is the definition of GO:0140660, which dynein/dynactin binding terms do not capture. Consistent with the NEW annotation on human BICD2. Falcon deep research additionally cites independent reconstitution of full-length fly BicD-Egl with K10 mRNA (Sladewski et al. 2018) showing RNA-triggered opening of autoinhibited BicD and robust dynein-dynactin motility. Supporting Evidence: PMID:29944118 The hairy RNA significantly increased the number of processive movements of dynein in the presence of dynactin and Egl/DmBicD PMID:29944118 A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin PMID:32378283 The dynein adaptor Drosophila Bicaudal D (BicD) is auto-inhibited and activates dynein motility only after cargo is bound file:DROME/BicD/BicD-deep-research-falcon.md Addition of **K10 mRNA** opened the complex and produced robust minus-end-directed motility |
| GO:0007097 nuclear migration | IMP PMID:15582780 The Ste20-like kinase misshapen functions together with Bica... | NEW | Summary: BicD is required for apical migration of photoreceptor (R-cell) precursor nuclei in the eye disc and for nuclear localization in the developing nervous system. Reason: Participation: BicD is the dynein adaptor/activator whose phosphorylation-dependent apical accumulation, together with dynein, is required for dynein-driven apical R-cell nuclear migration, so it contributes part of the motor machinery that moves the nucleus rather than being a passive requirement. The cargo linkage to the nucleus in R cells is not defined (Klarsicht is the KASH protein there). Comparator: Dhc64C carries nuclear migration (IBA) and human BICD2 carries nuclear migration (NEW, IMP). Evidence is from abstracts only (Houalla 2005, Swan 1999), so this is proposed at the general term. Supporting Evidence: PMID:15582780 Bicaudal-D (Bic-D), an evolutionarily conserved dynein-interacting protein, is required for developmental control of nuclear migration in Drosophila PMID:15582780 Msn, like Bic-D, is required for the apical migration of differentiating R-cell precursor nuclei PMID:15582780 Msn increases the phosphorylation of Bic-D, which appears to be necessary for the apical accumulation of both Bic-D and dynein in developing R-cell precursor cells PMID:10559989 DLis-1 and Bic-D are further required for nuclear localization in the developing nervous system |
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Download this section (compressed HTML)Q: What links BicD-dynein to the nucleus during apical R-cell nuclear migration - does BicD bind the KASH protein Klarsicht or a nuclear pore component (as human BICD2 binds nesprin-2 and RANBP2)?
Suggested experts: Drosophila eye developmental biologists, nuclear positioning cell biologists
Q: Is BicD directly required for migration or anchoring of the oocyte nucleus (the basis of the TAS annotation to GO:0007312), or is its effect via gurken mRNA localization?
Suggested experts: Drosophila oogenesis researchers
Experiment: Test whether BicD localizes to the photoreceptor precursor nuclear envelope and binds Klarsicht or Nup358 using proximity labelling and cargo-binding-domain point mutants (e.g. K730) in eye-disc clones, scoring apical nuclear migration.
Type: proximity labelling and mutant rescue
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Download this section (compressed HTML)Bicaudal D (BicD) encodes a cytoplasmic protein that links diverse cargo to the dynein/dynactin motor. Cargos like mRNAs, proteins and organelles are transported along microtubules. Through this mechanism the product of BicDcontrols spatial aspects of gene expression and polarity formation during development. Additionally, it supports physiology of differentiated polar cells and the function of the nervous system.
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