title: Protrudin serves as an adaptor molecule that connects KIF5 and its cargoes in vesicular transport during process formation.
abstract: Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin-KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin-KIF5 axis appears to be integral to neuronal function.
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812-8582, Japan.
authors: Fumiko
authors: F
authors: Matsuzaki
authors: Michiko
authors: M
authors: Shirane
authors: Masaki
authors: M
authors: Matsumoto
authors: Keiichi I
authors: KI
authors: Nakayama
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D022161:Transport Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000097573:Red Fluorescent Protein; D000099193:rab11 GTP-Binding Proteins
chemical_list: D002352:Carrier Proteins; D049452:Green Fluorescent Proteins; D016547:Kinesins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D000097573:Red Fluorescent Protein; D000099193:rab11 GTP-Binding Proteins; C500506:KIF5A protein, human; C490398:Kif1b protein, mouse; C507512:Kif5A protein, mouse; C476198:RTN3 protein, human; C548133:RTN3 protein, rat; C094364:SURF4 protein, human; C114051:VAPA protein, human; C529892:VAPB protein, mouse; C513390:ZFYVE27 protein, human; C485184:enhanced green fluorescent protein; C514783:protrudin protein, mouse; C475469:Kif5b protein, mouse