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GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4
BACKGROUND: Glycogen Synthase Kinase 3 (GSK3) has been implicated in regulating chromosomal alignment and mitotic progression but the physiological substrates mediating these GSK3-dependent effects have not been identified. Collapsin Response Mediator Protein 4 (CRMP4) is a cytosolic phosphoprotein...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002381/ https://www.ncbi.nlm.nih.gov/pubmed/21179545 http://dx.doi.org/10.1371/journal.pone.0014345 |
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author | Ong Tone, Stephan Dayanandan, Bama Fournier, Alyson E. Mandato, Craig A. |
author_facet | Ong Tone, Stephan Dayanandan, Bama Fournier, Alyson E. Mandato, Craig A. |
author_sort | Ong Tone, Stephan |
collection | PubMed |
description | BACKGROUND: Glycogen Synthase Kinase 3 (GSK3) has been implicated in regulating chromosomal alignment and mitotic progression but the physiological substrates mediating these GSK3-dependent effects have not been identified. Collapsin Response Mediator Protein 4 (CRMP4) is a cytosolic phosphoprotein known to regulate cytoskeletal dynamics and is a known physiological substrate of GSK3. In this study, we investigate the role of CRMP4 during mitosis. METHODOLOGY AND PRINCIPAL FINDINGS: Here we demonstrate that during mitosis CRMP4 phosphorylation is regulated in a GSK3-dependent manner. We show that CRMP4 localizes to spindle microtubules during mitosis and loss of CRMP4 disrupts chromosomal alignment and mitotic progression. The effect of CRMP4 on chromosomal alignment is dependent on phosphorylation by GSK3 identifying CRMP4 as a critical GSK3 substrate during mitotic progression. We also provide mechanistic data demonstrating that CRMP4 regulates spindle microtubules consistent with its known role in the regulation of the microtubule cytoskeleton. CONCLUSION AND SIGNIFICANCE: Our findings identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules. |
format | Text |
id | pubmed-3002381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30023812010-12-21 GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 Ong Tone, Stephan Dayanandan, Bama Fournier, Alyson E. Mandato, Craig A. PLoS One Research Article BACKGROUND: Glycogen Synthase Kinase 3 (GSK3) has been implicated in regulating chromosomal alignment and mitotic progression but the physiological substrates mediating these GSK3-dependent effects have not been identified. Collapsin Response Mediator Protein 4 (CRMP4) is a cytosolic phosphoprotein known to regulate cytoskeletal dynamics and is a known physiological substrate of GSK3. In this study, we investigate the role of CRMP4 during mitosis. METHODOLOGY AND PRINCIPAL FINDINGS: Here we demonstrate that during mitosis CRMP4 phosphorylation is regulated in a GSK3-dependent manner. We show that CRMP4 localizes to spindle microtubules during mitosis and loss of CRMP4 disrupts chromosomal alignment and mitotic progression. The effect of CRMP4 on chromosomal alignment is dependent on phosphorylation by GSK3 identifying CRMP4 as a critical GSK3 substrate during mitotic progression. We also provide mechanistic data demonstrating that CRMP4 regulates spindle microtubules consistent with its known role in the regulation of the microtubule cytoskeleton. CONCLUSION AND SIGNIFICANCE: Our findings identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules. Public Library of Science 2010-12-15 /pmc/articles/PMC3002381/ /pubmed/21179545 http://dx.doi.org/10.1371/journal.pone.0014345 Text en Ong Tone et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ong Tone, Stephan Dayanandan, Bama Fournier, Alyson E. Mandato, Craig A. GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title | GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title_full | GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title_fullStr | GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title_full_unstemmed | GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title_short | GSK3 Regulates Mitotic Chromosomal Alignment through CRMP4 |
title_sort | gsk3 regulates mitotic chromosomal alignment through crmp4 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002381/ https://www.ncbi.nlm.nih.gov/pubmed/21179545 http://dx.doi.org/10.1371/journal.pone.0014345 |
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