title: The axonal transport motor kinesin-2 navigates microtubule obstacles via protofilament switching.
abstract: Axonal transport involves kinesin motors trafficking cargo along microtubules that are rich in microtubule-associated proteins (MAPs). Much attention has focused on the behavior of kinesin-1 in the presence of MAPs, which has overshadowed understanding the contribution of other kinesins such as kinesin-2 in axonal transport. We have previously shown that, unlike kinesin-1, kinesin-2 in vitro motility is insensitive to the neuronal MAP Tau. However, the mechanism by which kinesin-2 efficiently navigates Tau on the microtubule surface is unknown. We hypothesized that mammalian kinesin-2 side-steps to adjacent protofilaments to maneuver around MAPs. To test this, we used single-molecule imaging to track the characteristic run length and protofilament switching behavior of kinesin-1 and kinesin-2 motors in the absence and presence of 2 different microtubule obstacles. Under all conditions tested, kinesin-2 switched protofilaments more frequently than kinesin-1. Using computational modeling that recapitulates run length and switching frequencies in the presence of varying roadblock densities, we conclude that kinesin-2 switches protofilaments to navigate around microtubule obstacles. Elucidating the kinesin-2 mechanism of navigation on the crowded microtubule surface provides a refined view of its contribution in facilitating axonal transport.
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Vermont, Burlington, Vermont.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Hoeprich
authors.affiliation: Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania.|Intercollege Graduate Degree Program in Bioengineering, Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Mickolajczyk
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Vermont, Burlington, Vermont.
authors.forename: Shane R
authors.initials: SR
authors.lastname: Nelson
authors.affiliation: Department of Biomedical Engineering, Pennsylvania State University, University Park, Pennsylvania.
authors.forename: William O
authors.identifier: 0000-0001-5547-8755
authors.initials: WO
authors.lastname: Hancock
authors.affiliation: Department of Molecular Physiology & Biophysics, University of Vermont, Burlington, Vermont.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Berger
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002417:Cattle; D003198:Computer Simulation; D003599:Cytoskeleton / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D016875:tau Proteins / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D016875:tau Proteins; C074152:kinesin-II; D016547:Kinesins
keywords: kinesin; microtubule; motility; protofilament; tau