Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway
| Autor: | Dirk Geerts, Peter L. Hordijk, Paul J. Hensbergen, Eloise C. Anthony, Gudula Schmidt, Mar Fernandez-Borja, Micha Nethe, André M. Deelder, Rob Dee |
|---|---|
| Přispěvatelé: | Hematology laboratory, Physiology, Landsteiner Laboratory, Cancer Center Amsterdam, Oncogenomics |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
rac1 GTP-Binding Protein
Small interfering RNA RHOA Caveolin 1 RAC1 CDC42 Focal adhesion Small hairpin RNA Mice Cell Movement Animals Humans RNA Small Interfering Feedback Physiological Focal Adhesions Microscopy Confocal biology Effector Cell Biology Fibroblasts Actin cytoskeleton Actins Cell biology Pyrones Quinolines biology.protein Cell Surface Extensions Rac1GTPase Caveolin-1 Adhesion Ubiquitylation cytotoxic necrotizing factor-1 rho-gtpase activation cell-migration phosphorylated caveolin-1 membrane domains polybasic region terminal domain degradation rac1 proteins HeLa Cells |
| Zdroj: | Journal of Cell Science, 123(11), 1948-1958 Journal of Cell Science, 123(Pt 11), 1948-58. Company of Biologists Ltd Journal of Cell Science, 123(11), 1948-1958. Company of Biologists Ltd Nethe, M, Anthony, E C, Fernandez-Borja, M, Dee, R, Geerts, D, Hensbergen, P J, Deelder, A M, Schmidt, G & Hordijk, P L 2010, ' Focal-adhesion targeting links caveolin-1 to a Rac1-degradation pathway ', Journal of Cell Science, vol. 123, no. 11, pp. 1948-1958 . https://doi.org/10.1242/jcs.062919 Journal of cell science, 123(11), 1948-1958. Company of Biologists Ltd |
| ISSN: | 0021-9533 |
| Popis: | Directional cell migration is crucially dependent on the spatiotemporal control of intracellular signalling events. These events regulate polarized actin dynamics, resulting in protrusion at the front of the cell and contraction at the rear. The actin cytoskeleton is regulated through signalling by Rho-like GTPases, such as RhoA, which stimulates myosin-based contractility, and CDC42 and Rac1, which promote actin polymerization and protrusion. Here, we show that Rac1 binds the adapter protein caveolin-1 (Cav1) and that Rac1 activity promotes Cav1 accumulation at Rac1-positive peripheral adhesions. Using Cav1-deficient mouse fibroblasts and depletion of Cav1 expression in human epithelial and endothelial cells mediated by small interfering RNA and short hairpin RNA, we show that loss of Cav1 induces an increase in Rac1 protein and its activated, GTP-bound form. Cav1 controls Rac1 protein levels by regulating ubiquitylation and degradation of activated Rac1 in an adhesion-dependent fashion. Finally, we show that Rac1 ubiquitylation is not required for effector binding, but regulates the dynamics of Rac1 at the periphery of the cell. These data extend the canonical model of Rac1 inactivation and uncover Cav1-regulated polyubiquitylation as an additional mechanism to control Rac1 signalling. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|