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High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport

The specific physiological roles of dynein regulatory factors remain poorly understood as a result of their functional complexity and the interdependence of dynein and kinesin motor activities. We used a novel approach to overcome these challenges, combining acute in vivo inhibition with automated h...

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Detalles Bibliográficos
Autores principales: Yi, Julie Y., Ori-McKenney, Kassandra M., McKenney, Richard J., Vershinin, Michael, Gross, Steven P., Vallee, Richard B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198168/
https://www.ncbi.nlm.nih.gov/pubmed/22006948
http://dx.doi.org/10.1083/jcb.201104076
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author Yi, Julie Y.
Ori-McKenney, Kassandra M.
McKenney, Richard J.
Vershinin, Michael
Gross, Steven P.
Vallee, Richard B.
author_facet Yi, Julie Y.
Ori-McKenney, Kassandra M.
McKenney, Richard J.
Vershinin, Michael
Gross, Steven P.
Vallee, Richard B.
author_sort Yi, Julie Y.
collection PubMed
description The specific physiological roles of dynein regulatory factors remain poorly understood as a result of their functional complexity and the interdependence of dynein and kinesin motor activities. We used a novel approach to overcome these challenges, combining acute in vivo inhibition with automated high temporal and spatial resolution particle tracking. Acute dynein inhibition in nonneuronal cells caused an immediate dispersal of diverse forms of cargo, resulting from a sharp decrease in microtubule minus-end run length followed by a gradual decrease in plus-end runs. Acute LIS1 inhibition or LIS1 RNA interference had little effect on lysosomes/late endosomes but severely inhibited axonal transport of large, but not small, vesicular structures. Our acute inhibition results argue against direct mechanical activation of opposite-directed motors and offer a novel approach of potential broad utility in the study of motor protein function in vivo. Our data also reveal a specific but cell type–restricted role for LIS1 in large vesicular transport and provide the first quantitative support for a general role for LIS1 in high-load dynein functions.
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spelling pubmed-31981682012-04-17 High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport Yi, Julie Y. Ori-McKenney, Kassandra M. McKenney, Richard J. Vershinin, Michael Gross, Steven P. Vallee, Richard B. J Cell Biol Research Articles The specific physiological roles of dynein regulatory factors remain poorly understood as a result of their functional complexity and the interdependence of dynein and kinesin motor activities. We used a novel approach to overcome these challenges, combining acute in vivo inhibition with automated high temporal and spatial resolution particle tracking. Acute dynein inhibition in nonneuronal cells caused an immediate dispersal of diverse forms of cargo, resulting from a sharp decrease in microtubule minus-end run length followed by a gradual decrease in plus-end runs. Acute LIS1 inhibition or LIS1 RNA interference had little effect on lysosomes/late endosomes but severely inhibited axonal transport of large, but not small, vesicular structures. Our acute inhibition results argue against direct mechanical activation of opposite-directed motors and offer a novel approach of potential broad utility in the study of motor protein function in vivo. Our data also reveal a specific but cell type–restricted role for LIS1 in large vesicular transport and provide the first quantitative support for a general role for LIS1 in high-load dynein functions. The Rockefeller University Press 2011-10-17 /pmc/articles/PMC3198168/ /pubmed/22006948 http://dx.doi.org/10.1083/jcb.201104076 Text en © 2011 Yi et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Yi, Julie Y.
Ori-McKenney, Kassandra M.
McKenney, Richard J.
Vershinin, Michael
Gross, Steven P.
Vallee, Richard B.
High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title_full High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title_fullStr High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title_full_unstemmed High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title_short High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport
title_sort high-resolution imaging reveals indirect coordination of opposite motors and a role for lis1 in high-load axonal transport
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198168/
https://www.ncbi.nlm.nih.gov/pubmed/22006948
http://dx.doi.org/10.1083/jcb.201104076
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