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...
Main Authors: | , , , |
---|---|
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 |
_version_ | 1818217897393127424 |
---|---|
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. |
first_indexed | 2024-12-12T07:15:10Z |
format | Article |
id | doaj.art-a5cdcbc01fc943c1a59d1941986432d1 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-12T07:15:10Z |
publishDate | 2010-12-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT stephanongtone gsk3regulatesmitoticchromosomalalignmentthroughcrmp4 AT bamadayanandan gsk3regulatesmitoticchromosomalalignmentthroughcrmp4 AT alysonefournier gsk3regulatesmitoticchromosomalalignmentthroughcrmp4 AT craigamandato gsk3regulatesmitoticchromosomalalignmentthroughcrmp4 |