TY - JOUR
T1 - The axonal transport motor kinesin-2 navigates microtubule obstacles via protofilament switching
AU - Hoeprich, Gregory J.
AU - Mickolajczyk, Keith J.
AU - Nelson, Shane R.
AU - Hancock, William O.
AU - Berger, Christopher L.
N1 - Funding Information:
The authors thank Dr. David Warshaw and Guy Kennedy for equipment, operational support and helpful discussions. Also, Dr. Jason Stumpff and Dr. M. Yusuf Ali for helpful discussions during preparation of the manuscript. No conflicts of interest. This work was supported by the National Institutes of Health (R01-GM-101066 to C.L.B. and R01-GM-076476 to W.O.H.). The Editorial Process File is available in the online version of this article.
Publisher Copyright:
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2017/5/1
Y1 - 2017/5/1
N2 - 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.
AB - 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.
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U2 - 10.1111/tra.12478
DO - 10.1111/tra.12478
M3 - Article
C2 - 28267259
AN - SCOPUS:85017193744
VL - 18
SP - 304
EP - 314
JO - Traffic
JF - Traffic
SN - 1398-9219
IS - 5
ER -