Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration
| Autor: | Claire M. Wells, Steen K.T. Ooi, Marita J. Walmsley, Victor L. J. Tybulewicz, Anne J. Ridley |
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| Rok vydání: | 2004 |
| Předmět: |
rac1 GTP-Binding Protein
DNA Complementary Membrane ruffling Gene Expression Motility Rac3 RAC1 CDC42 In Vitro Techniques Biology Cell morphology Nuclear Receptor Coactivator 3 Mice Cell Movement Cell Adhesion Animals Macrophage Mice Knockout Base Sequence Macrophage Colony-Stimulating Factor Macrophages Cell Membrane Cell migration Cell Biology rac GTP-Binding Proteins Cell biology Mice Inbred C57BL Phenotype Transcription Factors |
| Zdroj: | Journal of Cell Science. 117:1259-1268 |
| ISSN: | 1477-9137 0021-9533 |
| Popis: | Rac GTPases are activated by extracellular stimuli and contribute to cellular responses including cytoskeletal changes and cell migration. Dominant-negative Rac1 has been used to implicate Rac GTPases in these responses, but which of the three mammalian Rac isoforms it inhibits is not known. We show that mouse bone marrow-derived macrophages express Rac1, low levels of Rac2 but not Rac3. As Rac1-null mice die early in development, we have used mice with a loxP-flanked allele of Rac1 and the type I interferon-inducible Mx1-Cre transgene to address for the first time the specific role of Rac1 in cell motility. Bone marrow-derived macrophages isolated from mice treated with polyIC to induce interferon lack detectable Rac1, and there is no compensatory increase in Rac2 or Cdc42 expression. Rac1-deficient macrophages have an altered morphology: they are significantly more elongated than control cells and have a reduced adhesive area. Re-expression of Rac1 reverts the morphology to that of control cells. Loss of Rac1 reduces but does not completely prevent membrane ruffling in response to CSF-1. However, Rac1-deficient macrophages show normal migration and chemotaxis. Thus in macrophages Rac1 is primarily responsible for regulating cell morphology, contributes to membrane ruffling, but is not required for migration. |
| Databáze: | OpenAIRE |
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