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LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains

Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulte...

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Autores principales: Ou, Sirong, Tan, Mei-Hua, Weng, Ting, Li, HoiYeung, Koh, Cheng-Gee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030115/
https://www.ncbi.nlm.nih.gov/pubmed/29925632
http://dx.doi.org/10.1098/rsob.170202
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author Ou, Sirong
Tan, Mei-Hua
Weng, Ting
Li, HoiYeung
Koh, Cheng-Gee
author_facet Ou, Sirong
Tan, Mei-Hua
Weng, Ting
Li, HoiYeung
Koh, Cheng-Gee
author_sort Ou, Sirong
collection PubMed
description Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulted in multi-polar spindles and defocusing of centrosomes, implicating its involvement in the regulation of mitotic centrosome integrity. LIMK1 could influence centrosome integrity by modulating centrosomal protein localization at the spindle pole. Interestingly, dynein light intermediate chains (LICs) are able to rescue the defects observed in LIMK1-depleted cells. We found that LICs are potential novel interacting partners and substrates of LIMK1 and that LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity.
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spelling pubmed-60301152018-07-17 LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains Ou, Sirong Tan, Mei-Hua Weng, Ting Li, HoiYeung Koh, Cheng-Gee Open Biol Research Abnormal centrosome number and function have been implicated in tumour development. LIM kinase1 (LIMK1), a regulator of actin cytoskeleton dynamics, is found to localize at the mitotic centrosome. However, its role at the centrosome is not fully explored. Here, we report that LIMK1 depletion resulted in multi-polar spindles and defocusing of centrosomes, implicating its involvement in the regulation of mitotic centrosome integrity. LIMK1 could influence centrosome integrity by modulating centrosomal protein localization at the spindle pole. Interestingly, dynein light intermediate chains (LICs) are able to rescue the defects observed in LIMK1-depleted cells. We found that LICs are potential novel interacting partners and substrates of LIMK1 and that LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity. The Royal Society 2018-06-20 /pmc/articles/PMC6030115/ /pubmed/29925632 http://dx.doi.org/10.1098/rsob.170202 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Ou, Sirong
Tan, Mei-Hua
Weng, Ting
Li, HoiYeung
Koh, Cheng-Gee
LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title_full LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title_fullStr LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title_full_unstemmed LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title_short LIM kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
title_sort lim kinase1 regulates mitotic centrosome integrity via its activity on dynein light intermediate chains
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030115/
https://www.ncbi.nlm.nih.gov/pubmed/29925632
http://dx.doi.org/10.1098/rsob.170202
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