Letter abstract
Nature Cell Biology 7, 901 - 908 (2005)
Published online: 21 August 2005 | doi:10.1038/ncb1293
Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization
Miguel A. del Pozo1, Nagaraj Balasubramanian2, Nazilla B. Alderson1, William B. Kiosses3, Araceli Grande-García1, Richard G. W. Anderson4 & Martin A. Schwartz2
Growth of normal cells is anchorage dependent because signalling through multiple pathways including Erk, phosphatidylinositol-3-OH kinase (PI(3)K) and Rac requires integrin-mediated cell adhesion1. Components of these pathways localize to low-density, cholesterol-rich domains in the plasma membrane named 'lipid rafts'2, 3 or 'cholesterol-enriched membrane microdomains' (CEMM)4. We previously reported that integrin-mediated adhesion regulates CEMM transport such that cell detachment from the extracellular matrix triggers CEMM internalization and clearance from the plasma membrane5. We now report that this internalization is mediated by dynamin-2 and caveolin-1. Internalization requires phosphorylation of caveolin-1 on Tyr 14. A shift in localization of phospho-caveolin-1 from focal adhesions to caveolae induces CEMM internalization upon cell detachment, which mediates inhibition of Erk, PI(3)K and Rac. These data define a novel molecular mechanism for growth and tumour suppression by caveolin-1.
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
- Departments of Microbiology and Biomedical Engineering, Mellon Prostate Cancer Research Institute and Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, USA.
- Microscopy Facility, The Scripps Research Institute, La Jolla, CA 92037, USA.
- Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Correspondence to: Miguel A. del Pozo1 e-mail: madelpozo@cnic.es
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