title: Regulation of zipcode binding protein 1 transport dynamics in axons by myosin Va.
abstract: Directed transport of the mRNA binding protein, zipcode binding protein1 (ZBP1), into developing axons is believed to play an important role in mRNA localization and local protein synthesis. The role of molecular motors in this process is unclear. We elucidated a role for myosin Va (MyoVa) to modulate the axonal localization and transport of ZBP1 in axons. Using cultured rat hippocampal neurons, ZBP1 colocalized with MyoVa in axons and growth cones. Interaction of MyoVa with ZBP1 was evident by coimmunoprecipitation of endogenous and overexpressed proteins. Inhibition of MyoVa function with the globular tail domain (GTD) of MyoVa protein or short hairpin RNA led to an accumulation of ZBP1 in axons. Live cell imaging of mCherryZBP1 in neurons expressing GTD showed an increase in the number of motile particles, run length, and stimulated anterograde moving ZBP1 particles, suggesting that MyoVa controls availability of ZBP1 for microtubule-dependent transport. These findings suggest a novel regulatory role for MyoVa in the transport of ZBP1 within axons.
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Vijayalaxmi C
authors.initials: VC
authors.lastname: Nalavadi
authors.forename: Laura E
authors.initials: LE
authors.lastname: Griffin
authors.forename: Philip
authors.initials: P
authors.lastname: Picard-Fraser
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Swanson
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bassell
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D005260:Female; D020439:Growth Cones / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D017711:Nonlinear Dynamics; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: C498634:Igf2bp1 protein, rat; D008164:Luminescent Proteins; C513081:Myo5a protein, rat; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D024701:Myosin Type V; D018995:Myosin Heavy Chains