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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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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 »
Inhibition of Integrin-mediated Cell Adhesion but Not Directional Cell Migration Requires Catalytic Activity of EphB3 Receptor Tyrosine Kinase: ROLE OF RHO FAMILY SMALL GTPases.
H. Miao, K. Strebhardt, E. B. Pasquale, T.-L. Shen, J.-L. Guan, and B. Wang (2005)
J. Biol. Chem. 280, 923-932
   Abstract »    Full Text »    PDF »
Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient.
M. Wysoczynski, R. Reca, J. Ratajczak, M. Kucia, N. Shirvaikar, M. Honczarenko, M. Mills, J. Wanzeck, A. Janowska-Wieczorek, and M. Z. Ratajczak (2005)
Blood 105, 40-48
   Abstract »    Full Text »    PDF »
Nef Associates with p21-Activated Kinase 2 in a p21-GTPase-Dependent Dynamic Activation Complex within Lipid Rafts.
K. Pulkkinen, G. H. Renkema, F. Kirchhoff, and K. Saksela (2004)
J. Virol. 78, 12773-12780
   Abstract »    Full Text »    PDF »
A role for caveolae in cell migration.
A. NAVARRO, B. ANAND-APTE, and M.-O. PARAT (2004)
FASEB J 18, 1801-1811
   Abstract »    Full Text »    PDF »
Syndecan-4 Regulates ATF-2 Transcriptional Activity in a Rac1-dependent Manner.
S. Saoncella, E. Calautti, W. Neveu, and P. F. Goetinck (2004)
J. Biol. Chem. 279, 47172-47176
   Abstract »    Full Text »    PDF »


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