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Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility
Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human mic...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172920/ https://www.ncbi.nlm.nih.gov/pubmed/12707310 http://dx.doi.org/10.1083/jcb.200209057 |
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author | Fischer, Robert S. Fritz-Six, Kimberly L. Fowler, Velia M. |
author_facet | Fischer, Robert S. Fritz-Six, Kimberly L. Fowler, Velia M. |
author_sort | Fischer, Robert S. |
collection | PubMed |
description | Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1). Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia. Transient overexpression of GFP–Tmod3 leads to a depolarized cell morphology and decreased cell motility. A fivefold increase in Tmod3 results in an equivalent decrease in free pointed ends in the cells. Unexpectedly, a decrease in the relative amounts of F-actin, free barbed ends, and actin-related protein 2/3 (Arp2/3) complex in lamellipodia are also observed. Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments. These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia. |
format | Text |
id | pubmed-2172920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21729202008-05-01 Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility Fischer, Robert S. Fritz-Six, Kimberly L. Fowler, Velia M. J Cell Biol Article Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1). Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia. Transient overexpression of GFP–Tmod3 leads to a depolarized cell morphology and decreased cell motility. A fivefold increase in Tmod3 results in an equivalent decrease in free pointed ends in the cells. Unexpectedly, a decrease in the relative amounts of F-actin, free barbed ends, and actin-related protein 2/3 (Arp2/3) complex in lamellipodia are also observed. Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments. These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia. The Rockefeller University Press 2003-04-28 /pmc/articles/PMC2172920/ /pubmed/12707310 http://dx.doi.org/10.1083/jcb.200209057 Text en Copyright © 2003, 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 | Article Fischer, Robert S. Fritz-Six, Kimberly L. Fowler, Velia M. Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title | Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title_full | Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title_fullStr | Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title_full_unstemmed | Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title_short | Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
title_sort | pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172920/ https://www.ncbi.nlm.nih.gov/pubmed/12707310 http://dx.doi.org/10.1083/jcb.200209057 |
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