GSK3 regulates mitotic chromosomal alignment through CRMP4.

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 reg...

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Main Authors: Stephan Ong Tone, Bama Dayanandan, Alyson E Fournier, Craig A Mandato
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-12-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3002381?pdf=render
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author Stephan Ong Tone
Bama Dayanandan
Alyson E Fournier
Craig A Mandato
author_facet Stephan Ong Tone
Bama Dayanandan
Alyson E Fournier
Craig A Mandato
author_sort Stephan Ong Tone
collection DOAJ
description 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.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.Our findings identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules.
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spelling doaj.art-a5cdcbc01fc943c1a59d1941986432d12022-12-22T00:33:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-12-01512e1434510.1371/journal.pone.0014345GSK3 regulates mitotic chromosomal alignment through CRMP4.Stephan Ong ToneBama DayanandanAlyson E FournierCraig A MandatoGlycogen 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.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.Our findings identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules.http://europepmc.org/articles/PMC3002381?pdf=render
spellingShingle Stephan Ong Tone
Bama Dayanandan
Alyson E Fournier
Craig A Mandato
GSK3 regulates mitotic chromosomal alignment through CRMP4.
PLoS ONE
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
url http://europepmc.org/articles/PMC3002381?pdf=render
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AT alysonefournier gsk3regulatesmitoticchromosomalalignmentthroughcrmp4
AT craigamandato gsk3regulatesmitoticchromosomalalignmentthroughcrmp4