Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes

Dianne Cox, Peter Chang, Qing Zhang, P. Gopal Reddy, Gary M. Bokoch, Steven Greenberg

Research output: Contribution to journalArticle

344 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1487-1494
Number of pages8
JournalJournal of Experimental Medicine
Volume186
Issue number9
DOIs
StatePublished - Nov 3 1997
Externally publishedYes

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methionyl-leucyl-phenylalanine
Macrophage Colony-Stimulating Factor
Fc Receptors
Phagocytosis
Chimerin 1
Acetates
Leukocytes
Formyl Peptide Receptor
Heterotrimeric GTP-Binding Proteins
rho GTP-Binding Proteins
Membranes
Actin Cytoskeleton
Actins
Immunoglobulin G
Macrophages
Peptides
phorbol-12-myristate
Inhibition (Psychology)
RAW 264.7 Cells

ASJC Scopus subject areas

  • Immunology

Cite this

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.

In: Journal of Experimental Medicine, Vol. 186, No. 9, 03.11.1997, p. 1487-1494.

Research output: Contribution to journalArticle

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. In: Journal of Experimental Medicine. 1997 ; Vol. 186, No. 9. pp. 1487-1494.
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