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.
Skip Nav Destination
Article navigation
3 November 1997
Article|
November 03 1997
Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes
Dianne Cox,
Dianne Cox
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
Peter Chang,
Peter Chang
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
Qing Zhang,
Qing Zhang
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
P. Gopal Reddy,
P. Gopal Reddy
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
Gary M. Bokoch,
Gary M. Bokoch
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
Steven Greenberg
Steven Greenberg
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Search for other works by this author on:
Dianne Cox
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Peter Chang
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Qing Zhang
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
P. Gopal Reddy
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Gary M. Bokoch
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Steven Greenberg
From the *Pulmonary Division, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032; and ‡Department of Immunology and Department of Cell Biology, Scripps Research Institute, La Jolla, California 92037
Address correspondence to Dr. Steven Greenberg, Columbia University, Department of Medicine, 630 West 168th St., New York, NY 10032. Phone: 212-305-1586; FAX: 212-305-1146; E-mail: [email protected]
1
Abbreviations used in this paper: Chimaerin-GAP, the GAP domain of n-chimaerin; IgG-RBCs, sheep erythrocytes opsonized with rabbit IgG; IPTG, isopropyl β-d-thiogalactopyranoside; RAW cells, RAW 264.7 mouse macrophage cell line.
Received:
June 23 1997
Revision Received:
September 05 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (9): 1487–1494.
Article history
Received:
June 23 1997
Revision Received:
September 05 1997
Citation
Dianne Cox, Peter Chang, Qing Zhang, P. Gopal Reddy, Gary M. Bokoch, Steven Greenberg; Requirements for Both Rac1 and Cdc42 in Membrane Ruffling and Phagocytosis in Leukocytes . J Exp Med 3 November 1997; 186 (9): 1487–1494. doi: https://doi.org/10.1084/jem.186.9.1487
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement