title: Bicaudal-D binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling.
abstract: Cargo transport by microtubule-based motors is essential for cell organisation and function. The Bicaudal-D (BicD) protein participates in the transport of a subset of cargoes by the minus-end-directed motor dynein, although the full extent of its functions is unclear. In this study, we report that in Drosophila zygotic BicD function is only obligatory in the nervous system. Clathrin heavy chain (Chc), a major constituent of coated pits and vesicles, is the most abundant protein co-precipitated with BicD from head extracts. BicD binds Chc directly and interacts genetically with components of the pathway for clathrin-mediated membrane trafficking. Directed transport and subcellular localisation of Chc is strongly perturbed in BicD mutant presynaptic boutons. Functional assays show that BicD and dynein are essential for the maintenance of normal levels of neurotransmission specifically during high-frequency electrical stimulation and that this is associated with a reduced rate of recycling of internalised synaptic membrane. Our results implicate BicD as a new player in clathrin-associated trafficking processes and show a novel requirement for microtubule-based motor transport in the synaptic vesicle cycle.
authors.affiliation: Cell Biology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuromi
authors.forename: Laura
authors.initials: L
authors.lastname: Briggs
authors.forename: David B
authors.initials: DB
authors.lastname: Green
authors.forename: João J
authors.initials: JJ
authors.lastname: Rocha
authors.forename: Sean T
authors.initials: ST
authors.lastname: Sweeney
authors.forename: Simon L
authors.initials: SL
authors.lastname: Bullock
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D033922:Clathrin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism; D004594:Electrophysiology; D007814:Larva / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009420:Nervous System / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: C061998:BicD protein, Drosophila; D029721:Drosophila Proteins; D033922:Clathrin Heavy Chains; D004398:Dyneins