title: Activation of conventional kinesin motors in clusters by Shaw voltage-gated K+ channels.
abstract: The conventional kinesin motor transports many different cargos to specific locations in neurons. How cargos regulate motor function remains unclear. Here we focus on KIF5, the heavy chain of conventional kinesin, and report that the Kv3 (Shaw) voltage-gated K(+) channel, the only known tetrameric KIF5-binding protein, clusters and activates KIF5 motors during axonal transport. Endogenous KIF5 often forms clusters along axons, suggesting a potential role of KIF5-binding proteins. Our biochemical assays reveal that the high-affinity multimeric binding between the Kv3.1 T1 domain and KIF5B requires three basic residues in the KIF5B tail. Kv3.1 T1 competes with the motor domain and microtubules, but not with kinesin light chain 1 (KLC1), for binding to the KIF5B tail. Live-cell imaging assays show that four KIF5-binding proteins, Kv3.1, KLC1 and two synaptic proteins SNAP25 and VAMP2, differ in how they regulate KIF5B distribution. Only Kv3.1 markedly increases the frequency and number of KIF5B-YFP anterograde puncta. Deletion of Kv3.1 channels reduces KIF5 clusters in mouse cerebellar neurons. Therefore, clustering and activation of KIF5 motors by Kv3 regulate the motor number in carrier vesicles containing the channel proteins, contributing not only to the specificity of Kv3 channel transport, but also to the cargo-mediated regulation of motor function.
authors.affiliation: Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Barry
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Xu
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Gu
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Dangel
authors.forename: Peter
authors.initials: P
authors.lastname: Jukkola
authors.forename: Chandra
authors.initials: C
authors.lastname: Shrestha
authors.forename: Chen
authors.initials: C
authors.lastname: Gu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D051670:Shaw Potassium Channels / Q000235:genetics / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: C521566:KIF5B protein, rat; C490839:Kcnc1 protein, mouse; C000715690:Klc1 protein, rat; C000715695:Kns2 protein, mouse; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D051670:Shaw Potassium Channels; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; C494706:Vamp2 protein, rat; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; C475469:Kif5b protein, mouse; D016547:Kinesins
keywords: Axonal transport; Cargo-motor interaction; Kinesin light chain; Molecular motor; Synaptic protein; Voltage-gated potassium channel