Research Article 2027 Activation of conventional kinesin motors in clusters by Shaw voltage-gated K+ channels Joshua Barry1, Mingxuan Xu2,*, Yuanzheng Gu2, Andrew W. Dangel3, Peter Jukkola4, Chandra Shrestha2,` and Chen Gu1,2,4,§ 1Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA 2Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA 3Plant-Microbe Genomics Facility, The Ohio State University, Columbus, OH 43210, USA 4Integrated Biomedical Graduate Program, The Ohio State University, Columbus, OH 43210, USA *Present address: Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA `Present address: Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech University, Blacksburg, VA 24061, USA §Author for correspondence (
[email protected]) Accepted 19 February 2013 Journal of Cell Science 126, 2027–2041 ß 2013. Published by The Company of Biologists Ltd doi: 10.1242/jcs.122234 Summary 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.