title: Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility.
abstract: Neuronal development, function and repair critically depend on axonal transport of vesicles and protein complexes, which is mediated in part by the molecular motor kinesin-1. Adaptor proteins recruit kinesin-1 to vesicles via direct association with kinesin heavy chain (KHC), the force-generating component, or via the accessory light chain (KLC). Binding of adaptors to the motor is believed to engage the motor for microtubule-based transport. We report that the adaptor protein Sunday Driver (syd, also known as JIP3 or JSAP1) interacts directly with KHC, in addition to and independently of its known interaction with KLC. Using an in vitro motility assay, we show that syd activates KHC for transport and enhances its motility, increasing both KHC velocity and run length. syd binding to KHC is functional in neurons, as syd mutants that bind KHC but not KLC are transported to axons and dendrites similarly to wild-type syd. This transport does not rely on syd oligomerization with itself or other JIP family members. These results establish syd as a positive regulator of kinesin activity and motility.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University in St Louis, School of Medicine, St Louis, MO, USA.
authors.forename: Faneng
authors.initials: F
authors.lastname: Sun
authors.forename: Chuanmei
authors.initials: C
authors.lastname: Zhu
authors.forename: Ram
authors.initials: R
authors.lastname: Dixit
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D019556:COS Cells; D002352:Carrier Proteins / Q000502:physiology*; D002522:Chlorocebus aethiops; D016547:Kinesins; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C411575:KIFC5 protein, mouse; C403619:Mapk8ip3 protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D016547:Kinesins