The axonal transport motor kinesin-2 navigates microtubule obstacles via protofilament switching

Gregory J. Hoeprich, Keith J. Mickolajczyk, Shane R. Nelson, William O. Hancock, Christopher L. Berger

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)304-314
Number of pages11
JournalTraffic
Volume18
Issue number5
DOIs
StatePublished - May 1 2017

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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