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Physiological role of the interaction between CARMIL1 and capping protein

The regulation of free barbed ends is central to the control of dynamic actin assembly and actin-based motility in cells. Capping protein (CP) is known to regulate barbed ends and control actin assembly in cells. The CARMIL family of proteins can bind and inhibit CP in vitro, but the physiological s...

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Detalles Bibliográficos
Autores principales: Edwards, Marc, Liang, Yun, Kim, Taekyung, Cooper, John A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784379/
https://www.ncbi.nlm.nih.gov/pubmed/23904264
http://dx.doi.org/10.1091/mbc.E13-05-0270
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author Edwards, Marc
Liang, Yun
Kim, Taekyung
Cooper, John A.
author_facet Edwards, Marc
Liang, Yun
Kim, Taekyung
Cooper, John A.
author_sort Edwards, Marc
collection PubMed
description The regulation of free barbed ends is central to the control of dynamic actin assembly and actin-based motility in cells. Capping protein (CP) is known to regulate barbed ends and control actin assembly in cells. The CARMIL family of proteins can bind and inhibit CP in vitro, but the physiological significance of the interaction of CARMIL with CP in cells is poorly understood. Mammalian cells lacking CARMIL1 have defects in lamellipodia, macropinocytosis, cell migration, and Rac1 activation. Here we investigate the physiological significance of the CARMIL1–CP interaction, using a point mutant with a well-defined biochemical defect. We find that the CARMIL1–CP interaction is essential for the assembly of lamellipodia, the formation of ruffles, and the process of macropinocytosis. In contrast, the interaction of CARMIL1 with CP shows little to no importance for other functions of CARMIL1, including localization of CARMIL1 to the membrane, activation of Rac1, and cell migration. One implication is that lamellipodia are only marginally important for cell migration in a wound-healing model. The results also suggest that the ability of CARMIL1 to inhibit CP in cells may be regulated.
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spelling pubmed-37843792013-12-16 Physiological role of the interaction between CARMIL1 and capping protein Edwards, Marc Liang, Yun Kim, Taekyung Cooper, John A. Mol Biol Cell Articles The regulation of free barbed ends is central to the control of dynamic actin assembly and actin-based motility in cells. Capping protein (CP) is known to regulate barbed ends and control actin assembly in cells. The CARMIL family of proteins can bind and inhibit CP in vitro, but the physiological significance of the interaction of CARMIL with CP in cells is poorly understood. Mammalian cells lacking CARMIL1 have defects in lamellipodia, macropinocytosis, cell migration, and Rac1 activation. Here we investigate the physiological significance of the CARMIL1–CP interaction, using a point mutant with a well-defined biochemical defect. We find that the CARMIL1–CP interaction is essential for the assembly of lamellipodia, the formation of ruffles, and the process of macropinocytosis. In contrast, the interaction of CARMIL1 with CP shows little to no importance for other functions of CARMIL1, including localization of CARMIL1 to the membrane, activation of Rac1, and cell migration. One implication is that lamellipodia are only marginally important for cell migration in a wound-healing model. The results also suggest that the ability of CARMIL1 to inhibit CP in cells may be regulated. The American Society for Cell Biology 2013-10-01 /pmc/articles/PMC3784379/ /pubmed/23904264 http://dx.doi.org/10.1091/mbc.E13-05-0270 Text en © 2013 Edwards et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Edwards, Marc
Liang, Yun
Kim, Taekyung
Cooper, John A.
Physiological role of the interaction between CARMIL1 and capping protein
title Physiological role of the interaction between CARMIL1 and capping protein
title_full Physiological role of the interaction between CARMIL1 and capping protein
title_fullStr Physiological role of the interaction between CARMIL1 and capping protein
title_full_unstemmed Physiological role of the interaction between CARMIL1 and capping protein
title_short Physiological role of the interaction between CARMIL1 and capping protein
title_sort physiological role of the interaction between carmil1 and capping protein
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784379/
https://www.ncbi.nlm.nih.gov/pubmed/23904264
http://dx.doi.org/10.1091/mbc.E13-05-0270
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