Cargando…

Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration

Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by LIM kinase (LIMK)–1-mediated phosphorylation and is reactivated by cofilin phosphatase Slingshot (SSH)-1L. In this study, we...

Descripción completa

Detalles Bibliográficos
Autores principales: Nishita, Michiru, Tomizawa, Chinatsu, Yamamoto, Masahiro, Horita, Yuji, Ohashi, Kazumasa, Mizuno, Kensaku
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171197/
https://www.ncbi.nlm.nih.gov/pubmed/16230460
http://dx.doi.org/10.1083/jcb.200504029
_version_ 1782144905060024320
author Nishita, Michiru
Tomizawa, Chinatsu
Yamamoto, Masahiro
Horita, Yuji
Ohashi, Kazumasa
Mizuno, Kensaku
author_facet Nishita, Michiru
Tomizawa, Chinatsu
Yamamoto, Masahiro
Horita, Yuji
Ohashi, Kazumasa
Mizuno, Kensaku
author_sort Nishita, Michiru
collection PubMed
description Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by LIM kinase (LIMK)–1-mediated phosphorylation and is reactivated by cofilin phosphatase Slingshot (SSH)-1L. In this study, we show that cofilin activity is temporally and spatially regulated by LIMK1 and SSH1L in chemokine-stimulated Jurkat T cells. The knockdown of LIMK1 suppressed chemokine-induced lamellipodium formation and cell migration, whereas SSH1L knockdown produced and retained multiple lamellipodial protrusions around the cell after cell stimulation and impaired directional cell migration. Our results indicate that LIMK1 is required for cell migration by stimulating lamellipodium formation in the initial stages of cell response and that SSH1L is crucially involved in directional cell migration by restricting the membrane protrusion to one direction and locally stimulating cofilin activity in the lamellipodium in the front of the migrating cell. We propose that LIMK1- and SSH1L-mediated spatiotemporal regulation of cofilin activity is critical for chemokine-induced polarized lamellipodium formation and directional cell movement.
format Text
id pubmed-2171197
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21711972008-03-05 Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration Nishita, Michiru Tomizawa, Chinatsu Yamamoto, Masahiro Horita, Yuji Ohashi, Kazumasa Mizuno, Kensaku J Cell Biol Research Articles Cofilin mediates lamellipodium extension and polarized cell migration by accelerating actin filament dynamics at the leading edge of migrating cells. Cofilin is inactivated by LIM kinase (LIMK)–1-mediated phosphorylation and is reactivated by cofilin phosphatase Slingshot (SSH)-1L. In this study, we show that cofilin activity is temporally and spatially regulated by LIMK1 and SSH1L in chemokine-stimulated Jurkat T cells. The knockdown of LIMK1 suppressed chemokine-induced lamellipodium formation and cell migration, whereas SSH1L knockdown produced and retained multiple lamellipodial protrusions around the cell after cell stimulation and impaired directional cell migration. Our results indicate that LIMK1 is required for cell migration by stimulating lamellipodium formation in the initial stages of cell response and that SSH1L is crucially involved in directional cell migration by restricting the membrane protrusion to one direction and locally stimulating cofilin activity in the lamellipodium in the front of the migrating cell. We propose that LIMK1- and SSH1L-mediated spatiotemporal regulation of cofilin activity is critical for chemokine-induced polarized lamellipodium formation and directional cell movement. The Rockefeller University Press 2005-10-24 /pmc/articles/PMC2171197/ /pubmed/16230460 http://dx.doi.org/10.1083/jcb.200504029 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Nishita, Michiru
Tomizawa, Chinatsu
Yamamoto, Masahiro
Horita, Yuji
Ohashi, Kazumasa
Mizuno, Kensaku
Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title_full Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title_fullStr Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title_full_unstemmed Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title_short Spatial and temporal regulation of cofilin activity by LIM kinase and Slingshot is critical for directional cell migration
title_sort spatial and temporal regulation of cofilin activity by lim kinase and slingshot is critical for directional cell migration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171197/
https://www.ncbi.nlm.nih.gov/pubmed/16230460
http://dx.doi.org/10.1083/jcb.200504029
work_keys_str_mv AT nishitamichiru spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration
AT tomizawachinatsu spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration
AT yamamotomasahiro spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration
AT horitayuji spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration
AT ohashikazumasa spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration
AT mizunokensaku spatialandtemporalregulationofcofilinactivitybylimkinaseandslingshotiscriticalfordirectionalcellmigration