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Science 6 February 2004:
Vol. 303. no. 5659, pp. 839 - 842
DOI: 10.1126/science.1092571
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Reports

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

Translocation of the small GTP-binding protein Rac1 to the cell plasma membrane is essential for activating downstream effectors and requires integrin-mediated adhesion of cells to extracellular matrix. We report that active Rac1 binds preferentially to low-density, cholesterol-rich membranes, and specificity is determined at least in part by membrane lipids. Cell detachment triggered internalization of plasma membrane cholesterol and lipid raft markers. Preventing internalization maintained Rac1 membrane targeting and effector activation in nonadherent cells. Regulation of lipid rafts by integrin signals may regulate the location of membrane domains such as lipid rafts and thereby control domain-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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Syndecans: New Kids on the Signaling Block.
E. Tkachenko, J. M. Rhodes, and M. Simons (2005)
Circ. Res. 96, 488-500
   Abstract »    Full Text »    PDF »
Integrin Engagement Differentially Modulates Epithelial Cell Motility by RhoA/ROCK and PAK1.
H. Zhou and R. H. Kramer (2005)
J. Biol. Chem. 280, 10624-10635
   Abstract »    Full Text »    PDF »
CXC Chemokine Ligand 12-Induced Focal Adhesion Kinase Activation and Segregation into Membrane Domains Is Modulated by Regulator of G Protein Signaling 1 in Pro-B Cells.
Y. Le, M. Honczarenko, A. M. Glodek, D. K. Ho, and L. E. Silberstein (2005)
J. Immunol. 174, 2582-2590
   Abstract »    Full Text »    PDF »
Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets.
S. Bodin, C. Soulet, H. Tronchere, P. Sie, C. Gachet, M. Plantavid, and B. Payrastre (2005)
J. Cell Sci. 118, 759-769
   Abstract »    Full Text »    PDF »
Vaccinia Virus Penetration Requires Cholesterol and Results in Specific Viral Envelope Proteins Associated with Lipid Rafts.
C.-S. Chung, C.-Y. Huang, and W. Chang (2005)
J. Virol. 79, 1623-1634
   Abstract »    Full Text »    PDF »
A role for Mer tyrosine kinase in {alpha}v{beta}5 integrin-mediated phagocytosis of apoptotic cells.
Y. Wu, S. Singh, M.-M. Georgescu, and R. B. Birge (2005)
J. Cell Sci. 118, 539-553
   Abstract »    Full Text »    PDF »
SH3 domain of spectrin participates in the activation of Rac in specialized calpain-induced integrin signaling complexes.
K. Bialkowska, T. C. Saido, and J. E. B. Fox (2005)
J. Cell Sci. 118, 381-395
   Abstract »    Full Text »    PDF »


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