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Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization
Kinesin-5 is a slow homotetrameric motor protein best known for its essential role in the mitotic spindle, where it limits the rate at which faster motors can move microtubules. In neurons, experimental suppression of kinesin-5 causes the axon to grow faster by increasing the mobility of microtubule...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279230/ https://www.ncbi.nlm.nih.gov/pubmed/25355946 http://dx.doi.org/10.1091/mbc.E14-08-1313 |
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author | Kahn, Olga I. Sharma, Vandana González-Billault, Christian Baas, Peter W. |
author_facet | Kahn, Olga I. Sharma, Vandana González-Billault, Christian Baas, Peter W. |
author_sort | Kahn, Olga I. |
collection | PubMed |
description | Kinesin-5 is a slow homotetrameric motor protein best known for its essential role in the mitotic spindle, where it limits the rate at which faster motors can move microtubules. In neurons, experimental suppression of kinesin-5 causes the axon to grow faster by increasing the mobility of microtubules in the axonal shaft and the invasion of microtubules into the growth cone. Does kinesin-5 act differently in dendrites, given that they have a population of minus end–distal microtubules not present in axons? Using rodent primary neurons in culture, we found that inhibition of kinesin-5 during various windows of time produces changes in dendritic morphology and microtubule organization. Specifically, dendrites became shorter and thinner and contained a greater proportion of minus end–distal microtubules, suggesting that kinesin-5 acting normally restrains the number of minus end–distal microtubules that are transported into dendrites. Additional data indicate that, in neurons, CDK5 is the kinase responsible for phosphorylating kinesin-5 at Thr-926, which is important for kinesin-5 to associate with microtubules. We also found that kinesin-5 associates preferentially with microtubules rich in tyrosinated tubulin. This is consistent with an observed accumulation of kinesin-5 on dendritic microtubules, as they are known to be less detyrosinated than axonal microtubules. |
format | Online Article Text |
id | pubmed-4279230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-42792302015-03-16 Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization Kahn, Olga I. Sharma, Vandana González-Billault, Christian Baas, Peter W. Mol Biol Cell Articles Kinesin-5 is a slow homotetrameric motor protein best known for its essential role in the mitotic spindle, where it limits the rate at which faster motors can move microtubules. In neurons, experimental suppression of kinesin-5 causes the axon to grow faster by increasing the mobility of microtubules in the axonal shaft and the invasion of microtubules into the growth cone. Does kinesin-5 act differently in dendrites, given that they have a population of minus end–distal microtubules not present in axons? Using rodent primary neurons in culture, we found that inhibition of kinesin-5 during various windows of time produces changes in dendritic morphology and microtubule organization. Specifically, dendrites became shorter and thinner and contained a greater proportion of minus end–distal microtubules, suggesting that kinesin-5 acting normally restrains the number of minus end–distal microtubules that are transported into dendrites. Additional data indicate that, in neurons, CDK5 is the kinase responsible for phosphorylating kinesin-5 at Thr-926, which is important for kinesin-5 to associate with microtubules. We also found that kinesin-5 associates preferentially with microtubules rich in tyrosinated tubulin. This is consistent with an observed accumulation of kinesin-5 on dendritic microtubules, as they are known to be less detyrosinated than axonal microtubules. The American Society for Cell Biology 2015-01-01 /pmc/articles/PMC4279230/ /pubmed/25355946 http://dx.doi.org/10.1091/mbc.E14-08-1313 Text en © 2015 Kahn et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Kahn, Olga I. Sharma, Vandana González-Billault, Christian Baas, Peter W. Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title | Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title_full | Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title_fullStr | Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title_full_unstemmed | Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title_short | Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
title_sort | effects of kinesin-5 inhibition on dendritic architecture and microtubule organization |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279230/ https://www.ncbi.nlm.nih.gov/pubmed/25355946 http://dx.doi.org/10.1091/mbc.E14-08-1313 |
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