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...
Autores principales: | , , , , , |
---|---|
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 |