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Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1

Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well un...

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Detalles Bibliográficos
Autores principales: Seth, Abhinav, Otomo, Chinatsu, Rosen, Michael K.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064313/
https://www.ncbi.nlm.nih.gov/pubmed/16943183
http://dx.doi.org/10.1083/jcb.200605006
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author Seth, Abhinav
Otomo, Chinatsu
Rosen, Michael K.
author_facet Seth, Abhinav
Otomo, Chinatsu
Rosen, Michael K.
author_sort Seth, Abhinav
collection PubMed
description Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor–mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function.
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spelling pubmed-20643132007-11-29 Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1 Seth, Abhinav Otomo, Chinatsu Rosen, Michael K. J Cell Biol Research Articles Diaphanous-related formins (DRFs) are key regulators of actin cytoskeletal dynamics whose in vitro actin assembly activities are thought to be regulated by autoinhibition. However, the in vivo consequences of autoinhibition and the involvement of DRFs in specific biological processes are not well understood. In this study, we show that in the DRFs FRLα (formin-related gene in leukocytes α) and mouse diaphanous 1, autoinhibition regulates a novel membrane localization activity in vivo as well as actin assembly activity in vitro. In FRLα, the Rho family guanosine triphosphatase Cdc42 relieves the autoinhibition of both membrane localization and biochemical actin assembly activities. FRLα is required for efficient Fc-γ receptor–mediated phagocytosis and is recruited to the phagocytic cup by Cdc42. These results suggest that mutual autoinhibition of biochemical activity and cellular localization may be a general regulatory principle for DRFs and demonstrate a novel role for formins in immune function. The Rockefeller University Press 2006-08-28 /pmc/articles/PMC2064313/ /pubmed/16943183 http://dx.doi.org/10.1083/jcb.200605006 Text en Copyright © 2006, 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
Seth, Abhinav
Otomo, Chinatsu
Rosen, Michael K.
Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title_full Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title_fullStr Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title_full_unstemmed Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title_short Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1
title_sort autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins frlα and mdia1
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064313/
https://www.ncbi.nlm.nih.gov/pubmed/16943183
http://dx.doi.org/10.1083/jcb.200605006
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