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Motor guidance by long-range communication on the microtubule highway

Coupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor–motor interactions. In contrast...

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Autores principales: Wijeratne, Sithara S., Fiorenza, Shane A., Neary, Alex E., Subramanian, Radhika, Betterton, Meredith D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282251/
https://www.ncbi.nlm.nih.gov/pubmed/35867749
http://dx.doi.org/10.1073/pnas.2120193119
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author Wijeratne, Sithara S.
Fiorenza, Shane A.
Neary, Alex E.
Subramanian, Radhika
Betterton, Meredith D.
author_facet Wijeratne, Sithara S.
Fiorenza, Shane A.
Neary, Alex E.
Subramanian, Radhika
Betterton, Meredith D.
author_sort Wijeratne, Sithara S.
collection PubMed
description Coupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor–motor interactions. In contrast, coupling mechanisms that act at longer length scales remain largely unexplored. Here we report that microtubules can physically couple motor movement in the absence of detectable short-range interactions. The human kinesin-4 Kif4A changes the run length and velocity of other motors on the same microtubule in the dilute binding limit, when approximately 10-nm–sized motors are much farther apart than the motor size. This effect does not depend on specific motor–motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micrometer-scale attractive interaction potential between motors is sufficient to recreate the experimental results in a biophysical model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling affects not only binding kinetics but also motor mechanochemistry. Therefore, the model predicts that motors can sense and respond to motors bound several micrometers away on a microtubule. Our results are consistent with a paradigm in which long-range motor interactions along the microtubule enable additional forms of collective motor behavior, possibly due to changes in the microtubule lattice.
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spelling pubmed-92822512023-01-07 Motor guidance by long-range communication on the microtubule highway Wijeratne, Sithara S. Fiorenza, Shane A. Neary, Alex E. Subramanian, Radhika Betterton, Meredith D. Proc Natl Acad Sci U S A Physical Sciences Coupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor–motor interactions. In contrast, coupling mechanisms that act at longer length scales remain largely unexplored. Here we report that microtubules can physically couple motor movement in the absence of detectable short-range interactions. The human kinesin-4 Kif4A changes the run length and velocity of other motors on the same microtubule in the dilute binding limit, when approximately 10-nm–sized motors are much farther apart than the motor size. This effect does not depend on specific motor–motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micrometer-scale attractive interaction potential between motors is sufficient to recreate the experimental results in a biophysical model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling affects not only binding kinetics but also motor mechanochemistry. Therefore, the model predicts that motors can sense and respond to motors bound several micrometers away on a microtubule. Our results are consistent with a paradigm in which long-range motor interactions along the microtubule enable additional forms of collective motor behavior, possibly due to changes in the microtubule lattice. National Academy of Sciences 2022-07-07 2022-07-12 /pmc/articles/PMC9282251/ /pubmed/35867749 http://dx.doi.org/10.1073/pnas.2120193119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Wijeratne, Sithara S.
Fiorenza, Shane A.
Neary, Alex E.
Subramanian, Radhika
Betterton, Meredith D.
Motor guidance by long-range communication on the microtubule highway
title Motor guidance by long-range communication on the microtubule highway
title_full Motor guidance by long-range communication on the microtubule highway
title_fullStr Motor guidance by long-range communication on the microtubule highway
title_full_unstemmed Motor guidance by long-range communication on the microtubule highway
title_short Motor guidance by long-range communication on the microtubule highway
title_sort motor guidance by long-range communication on the microtubule highway
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282251/
https://www.ncbi.nlm.nih.gov/pubmed/35867749
http://dx.doi.org/10.1073/pnas.2120193119
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