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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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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. |
format | Online Article Text |
id | pubmed-3198168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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