Research Article 3137 Engagement of CD81 induces ezrin tyrosine phosphorylation and its cellular redistribution with filamentous actin Greg P. Coffey1, Ranjani Rajapaksa1, Raymond Liu1, Orr Sharpe2, Chiung-Chi Kuo1, Sharon Wald Krauss3, Yael Sagi1, R. Eric Davis4, Louis M. Staudt4, Jeff P. Sharman1, William H. Robinson2 and Shoshana Levy1,* 1Stanford University, School of Medicine, Division of Oncology, Stanford, CA 94305, USA 2Stanford University, School of Medicine, Division of Immunology and Rheumatology, GRECC Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA 94304, USA 3Life Sciences Division, University of California Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA 4Metabolism Branch, National Cancer Institute, Bethesda, MD 20892, USA *Author for correspondence (
[email protected]) Accepted 10 June 2009 Journal of Cell Science 122, 3137-3144 Published by The Company of Biologists 2009 doi:10.1242/jcs.045658 Summary CD81 is a tetraspanin family member involved in diverse this association was disrupted when Syk activation was blocked. cellular interactions in the immune and nervous systems and Taken together, these studies suggest a model in which CD81 in cell fusion events. However, the mechanism of action of CD81 interfaces between the plasma membrane and the cytoskeleton and of other tetraspanins has not been defined. We reasoned by activating Syk, mobilizing ezrin, and recruiting F-actin to that identifying signaling molecules downstream of CD81 would facilitate cytoskeletal reorganization and cell signaling. This provide mechanistic clues. We engaged CD81 on the surface mechanism might explain the pleiotropic effects induced in of B-lymphocytes and identified the induced tyrosine- response to stimulation of cells by anti-CD81 antibodies or by phosphorylated proteins by mass spectrometry.