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Cited by 436Protein Kinase Regulation and GTPase SignalingCellular transport and secretionChemokine receptors and signaling

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

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Cox, Dianne, Chang, Peter, Zhang, Qing, Reddy, P. Gopal, Bokoch, Gary M., Greenberg, Steven·1997·The Journal of Experimental Medicine
DOI 10.1084/jem.186.9.1487PMC PMC2199122
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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.

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  • Actin assembly during phagocytosis is mediated by Rho family GTPases.

    “Experiments using clostridial toxins or transfection of dominant-negative constructs have convincingly demonstrated that actin assembly during phagocytosis is mediated by Rho family GTPases (Cox et al. 1997; Hackam et al. 1997; Caron and Hall 1998; Massol et al. 1998).”

    From Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis (2000) · cites this paper as Cox et al. 1997

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Research works printed but not linked: 25

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Authors
Cox, D., Chang, P., Zhang, Q., Reddy, P. G., Bokoch, G. M., & Greenberg, S.
Affiliations
Scripps Research Institute (US)
Corresponding author
Greenberg, Steven
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
1997-11-03
Volume
186
Issue
9
Pages
1487-1494
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.186.9.1487
PMC
PMC2199122
OpenAlex
W2093844155
Cited by
436
References
2
Citations by year
2026: 4 · 2025: 2 · 2024: 1 · 2023: 9 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 14 · 2015: 10 · 2014: 14 · 2013: 15 · 2012: 12
FWCI
9.62
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • American Cancer Society
  • American Heart Association
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL054164, HL 54164)
  • National Institute of General Medical Sciences (GM-44428, R01GM044428)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
Rac1, Cdc42, Rho GTPases, ruffles, phagocytosis, leukocyte motility, Fc gamma receptor, macrophages, actin cytoskeleton, chemotactic peptide receptor, fMLP, colony-stimulating factor 1, phorbol myristate acetate, phagocytic cup
MeSH terms
Animals, Cell Line, Cell Membrane, Cell Movement, Cytoskeleton, Humans, Macrophages, N-Formylmethionine Leucyl-Phenylalanine, Nerve Tissue Proteins, Phagocytosis, Proteins, Receptors, Immunologic, Tetradecanoylphorbol Acetate, Transfection, Macrophage Colony-Stimulating Factor, Receptors, IgG, Receptors, Peptide, Cell Cycle Proteins, GTP-Binding Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins, rac GTP-Binding Proteins, Chimerin 1, Receptors, Formyl Peptide, Mice

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