Heterogeneity in kinesin function

Babu J N Reddy; Suvranta Tripathy; Michael Vershinin; Marvin E Tanenbaum; Jing Xu; Michelle Mattson-Hoss; Karim Arabi; Dail Chapman; Tory Doolin; Changbong Hyeon; Steven P Gross

doi:10.1111/tra.12504

Heterogeneity in kinesin function

Babu J N Reddy, Suvranta Tripathy, Michael Vershinin, Marvin E Tanenbaum, Jing Xu, Michelle Mattson-Hoss, Karim Arabi, Dail Chapman, Tory Doolin, Changbong Hyeon, Steven P Gross

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

13 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	658-671
Number of pages	14
Journal	Traffic
Volume	18
Issue number	10
DOIs	https://doi.org/10.1111/tra.12504
Publication status	Published - Oct 2017

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Journal Article

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10.1111/tra.12504

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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 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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T1 - Heterogeneity in kinesin function

AU - Reddy, Babu J N

AU - Tripathy, Suvranta

AU - Vershinin, Michael

AU - Tanenbaum, Marvin E

AU - Xu, Jing

AU - Mattson-Hoss, Michelle

AU - Arabi, Karim

AU - Chapman, Dail

AU - Doolin, Tory

AU - Hyeon, Changbong

AU - Gross, Steven P

PY - 2017/10

Y1 - 2017/10

N2 - 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 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.

AB - 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 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.

KW - Journal Article

U2 - 10.1111/tra.12504

DO - 10.1111/tra.12504

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SN - 1398-9219

VL - 18

SP - 658

EP - 671

JO - Traffic

JF - Traffic

IS - 10

ER -

Heterogeneity in kinesin function

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