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Integrins Regulate Rac Targeting by Internalization of Membrane Domains
Miguel A. del Pozo,1,2,3*
Nazilla B. Alderson,1,2
William B. Kiosses,1
Hui-Hsien Chiang,1
Richard G. W. Anderson,4
Martin A. Schwartz1,5
Abstract:
Translocation of the small GTP-binding protein Rac1 to the cellplasma membrane is essential for activating downstream effectorsand requires integrin-mediated adhesion of cells to extracellularmatrix. We report that active Rac1 binds preferentially to low-density,cholesterol-rich membranes, and specificity is determined atleast in part by membrane lipids. Cell detachment triggeredinternalization of plasma membrane cholesterol and lipid raftmarkers. Preventing internalization maintained Rac1 membranetargeting and effector activation in nonadherent cells. Regulationof lipid rafts by integrin signals may regulate the locationof membrane domains such as lipid rafts and thereby controldomain-specific signaling events in anchorage-dependent cells.
1 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 2 Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. 3 Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. 4 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. 5 Departments of Microbiology and Biomedical Engineering, Mellon Prostate Cancer Research Institute and Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
* To whom correspondence should be addressed. E-mail: mdelpozo{at}scripps.edu
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Atorvastatin Restores Lck Expression and Lipid Raft-Associated Signaling in T Cells from Patients with Systemic Lupus Erythematosus.
E. C. Jury, D. A. Isenberg, C. Mauri, and M. R. Ehrenstein (2006)
J. Immunol.
177, 7416-7422
|Abstract »|Full Text »|PDF »
Plitidepsin Cellular Binding and Rac1/JNK Pathway Activation Depend on Membrane Cholesterol Content.
Y. Suarez, L. Gonzalez-Santiago, N. Zarich, A. Davalos, J. F. Aranda, M. A. Alonso, M. A. Lasuncion, J. M. Rojas, and A. Munoz (2006)
Mol. Pharmacol.
70, 1654-1663
|Abstract »|Full Text »|PDF »
Caveolin-Dependent Angiotensin II Type 1 Receptor Signaling in Vascular Smooth Muscle.
M. Ushio-Fukai and R. W. Alexander (2006)
Hypertension
48, 797-803
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Distinct Mechanisms of Clathrin-independent Endocytosis Have Unique Sphingolipid Requirements.
Z.-J. Cheng, R. D. Singh, D. K. Sharma, E. L. Holicky, K. Hanada, D. L. Marks, and R. E. Pagano (2006)
Mol. Biol. Cell
17, 3197-3210
|Abstract »|Full Text »|PDF »
D4-GDI, a Rho GTPase Regulator, Promotes Breast Cancer Cell Invasiveness.
