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 language | English (US) |
|---|---|
| Pages (from-to) | 1487-1494 |
| Number of pages | 8 |
| Journal | Journal of Experimental Medicine |
| Volume | 186 |
| Issue number | 9 |
| DOIs | |
| State | Published - Nov 3 1997 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Requirements for both Rac1 and Cdc42 in membrane ruffling and phagocytosis in leukocytes
AU - Cox, Dianne
AU - Chang, Peter
AU - Zhang, Qing
AU - Reddy, P. Gopal
AU - Bokoch, Gary M.
AU - Greenberg, Steven
PY - 1997/11/3
Y1 - 1997/11/3
N2 - 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.
AB - 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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U2 - 10.1084/jem.186.9.1487
DO - 10.1084/jem.186.9.1487
M3 - Article
VL - 186
SP - 1487
EP - 1494
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 9
ER -