Bicaudal-D binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling

TY - JOUR

T1 - Bicaudal-D binds clathrin heavy chain to promote its transport and augments synaptic vesicle recycling

AU - Li, Xuan

AU - Kuromi, Hiroshi

AU - Briggs, Laura

AU - Green, David B.

AU - Rocha, Joao J.

AU - Sweeney, Sean

AU - Bullock, Simon L.

PY - 2010/3/3

Y1 - 2010/3/3

N2 - 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. The EMBO Journal (2010) 29, 992-1006. doi: 10.1038/emboj.2009.410; Published online 28 January 2010

AB - 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. The EMBO Journal (2010) 29, 992-1006. doi: 10.1038/emboj.2009.410; Published online 28 January 2010

KW - BicD

KW - clathrin

KW - dynein

KW - microtubule-based transport

KW - synaptic vesicle recycling

KW - FROG NEUROMUSCULAR-JUNCTION

KW - MEDIATED ENDOCYTOSIS

KW - NEUROTRANSMITTER RELEASE

KW - DROSOPHILA OOGENESIS

KW - TRANSMITTER RELEASE

KW - CYTOPLASMIC DYNEIN

KW - MEMBRANE RETRIEVAL

KW - DYNACTIN COMPLEX

KW - COATED VESICLES

KW - EARLY ENDOSOMES

UR - http://www.scopus.com/inward/record.url?scp=77649339900&partnerID=8YFLogxK

U2 - 10.1038/emboj.2009.410

DO - 10.1038/emboj.2009.410

M3 - Article

VL - 29

SP - 992

EP - 1006

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 5

ER -