Heterogeneity in kinesin function
Reddy, Babu J.N.; Tripathy, Suvranta; Vershinin, Michael; Tanenbaum, Marvin E.; Xu, Jing; Mattson-Hoss, Michelle; Arabi, Karim; Chapman, Dail; Doolin, Tory; Hyeon, Changbong; Gross, Steven P.
(2017) Traffic, volume 18, issue 10, pp. 658 - 671
(Article)
Abstract
The kinesin family proteins are often studied as prototypical molecular motors; a deeper understanding of them can illuminate regulation of intracellular transport. It is typically assumed that they function identically. Here we find that this assumption of homogeneous function appears incorrect: variation among motors’ velocities in vivo and in vitro
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is larger than the stochastic variation expected for an ensemble of “identical” motors. When moving on microtubules, slow and fast motors are persistently slow, and fast, respectively. We develop theory that provides quantitative criteria to determine whether the observed single-molecule variation is too large to be generated from an ensemble of identical molecules. To analyze such heterogeneity, we group traces into homogeneous sub-ensembles. Motility studies varying the temperature, pH and glycerol concentration suggest at least 2 distinct functional states that are independently affected by external conditions. We end by investigating the functional ramifications of such heterogeneity through Monte-Carlo multi-motor simulations.
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Keywords: kinesin, kinesin velocity heterogeneity, molecular motors, proteins in glycerol and altered pH, temperature dependence of kinesin motility, Structural Biology, Biochemistry, Molecular Biology, Genetics, Cell Biology, Journal Article
ISSN: 1398-9219
Publisher: Blackwell Munksgaard
Note: Funding Information: C.H. thanks Anatoly Kolomeisky and Joe Howard for critical feedback on this work. S.P.G. was supported by NIH RO1 GM123068. Authors acknowledge Dr Siavash Ahrar, Physics Department, UC Irvine for the helpful technical and scientific discussions. Publisher Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
(Peer reviewed)