Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes

Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes

Specific pathways linking heterotrimeric G proteins and Fcγ receptors to the actin-based cytoskeleton are poorly understood. To test a requirement for Rho family members in cytoskeletal events mediated by structurally diverse receptors in leukocytes, we transfected the full-length human chemotactic...

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Main Authors: Cox, Dianne, Chang, Peter, Zhang, Qing, Reddy, P. Gopal, Bokoch, Gary M., Greenberg, Steven
Format: Online
Language:English
Published: The Rockefeller University Press 1997
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199122/
id pubmed-2199122
recordtype oai_dc
spelling pubmed-21991222008-04-16 Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes Cox, Dianne Chang, Peter Zhang, Qing Reddy, P. Gopal Bokoch, Gary M. Greenberg, Steven Article Specific pathways linking heterotrimeric G proteins and Fcγ receptors to the actin-based cytoskeleton are poorly understood. To test a requirement for Rho family members in cytoskeletal events mediated by structurally diverse receptors in leukocytes, we transfected the full-length human chemotactic peptide receptor in RAW 264.7 cells and examined cytoskeletal alterations in response to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), colony stimulating factor–1 (CSF-1), IgG-coated particles, and phorbol 12-myristate 13-acetate (PMA). Expression of Rac1 N17, Cdc42 N17, or the GAP domain of n-chimaerin inhibited cytoskeletal responses to FMLP and CSF-1, and blocked phagocytosis. Accumulation of F-actin– rich “phagocytic cups” was partially inhibited by expression of Rac1 N17 or Cdc42 N17. In contrast, PMA-induced ruffling was not inhibited by expression of Rac1 N17, but was blocked by expression of Cdc42 N17, indicating that cytoskeletal inhibition by these constructs was nonoverlapping. These results demonstrate differential requirements for Rho family GTPases in leukocyte motility, and indicate that both Rac1 and Cdc42 are required for Fcγ receptor– mediated phagocytosis and for membrane ruffling mediated by structurally distinct receptors in macrophages. The Rockefeller University Press 1997-11-03 /pmc/articles/PMC2199122/ /pubmed/9348306 Text en 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/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Cox, Dianne
Chang, Peter
Zhang, Qing
Reddy, P. Gopal
Bokoch, Gary M.
Greenberg, Steven
spellingShingle Cox, Dianne
Chang, Peter
Zhang, Qing
Reddy, P. Gopal
Bokoch, Gary M.
Greenberg, Steven
Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
author_facet Cox, Dianne
Chang, Peter
Zhang, Qing
Reddy, P. Gopal
Bokoch, Gary M.
Greenberg, Steven
author_sort Cox, Dianne
title Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
title_short Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
title_full Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
title_fullStr Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
title_full_unstemmed Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
title_sort requirements for both rac1 and cdc42 in membrane ruffling and phagocytosis in leukocytes
description Specific pathways linking heterotrimeric G proteins and Fcγ receptors to the actin-based cytoskeleton are poorly understood. To test a requirement for Rho family members in cytoskeletal events mediated by structurally diverse receptors in leukocytes, we transfected the full-length human chemotactic peptide receptor in RAW 264.7 cells and examined cytoskeletal alterations in response to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), colony stimulating factor–1 (CSF-1), IgG-coated particles, and phorbol 12-myristate 13-acetate (PMA). Expression of Rac1 N17, Cdc42 N17, or the GAP domain of n-chimaerin inhibited cytoskeletal responses to FMLP and CSF-1, and blocked phagocytosis. Accumulation of F-actin– rich “phagocytic cups” was partially inhibited by expression of Rac1 N17 or Cdc42 N17. In contrast, PMA-induced ruffling was not inhibited by expression of Rac1 N17, but was blocked by expression of Cdc42 N17, indicating that cytoskeletal inhibition by these constructs was nonoverlapping. These results demonstrate differential requirements for Rho family GTPases in leukocyte motility, and indicate that both Rac1 and Cdc42 are required for Fcγ receptor– mediated phagocytosis and for membrane ruffling mediated by structurally distinct receptors in macrophages.
publisher The Rockefeller University Press
publishDate 1997
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2199122/
_version_ 1611432800579223552

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