Engagement of CD81 induces ezrin tyrosine phosphorylation and its cellular redistribution with filamentous actin
Open Access
- 1 September 2009
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 122 (17), 3137-3144
- https://doi.org/10.1242/jcs.045658
Abstract
CD81 is a tetraspanin family member involved in diverse cellular interactions in the immune and nervous systems and in cell fusion events. However, the mechanism of action of CD81 and of other tetraspanins has not been defined. We reasoned that identifying signaling molecules downstream of CD81 would provide mechanistic clues. We engaged CD81 on the surface of B-lymphocytes and identified the induced tyrosine-phosphorylated proteins by mass spectrometry. This analysis showed that the most prominent tyrosine phosphorylated protein was ezrin, an actin-binding protein and a member of the ezrin-radixin-moesin family. We also found that CD81 engagement induces spleen tyrosine kinase (Syk) and that Syk was involved in tyrosine phosphorylation of ezrin. After engagement of CD81, it colocalized with ezrin and F-actin, and this association was disrupted when Syk activation was blocked. Taken together, these studies suggest a model in which CD81 interfaces between the plasma membrane and the cytoskeleton by activating Syk, mobilizing ezrin, and recruiting F-actin to facilitate cytoskeletal reorganization and cell signaling. This mechanism might explain the pleiotropic effects induced in response to stimulation of cells by anti-CD81 antibodies or by the hepatitis C virus, which uses this molecule as its key receptor.Keywords
This publication has 55 references indexed in Scilit:
- CD81 Is a Central Regulator of Cellular Events Required for Hepatitis C Virus Infection of Human HepatocytesJournal of Virology, 2008
- SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphomaPublished by American Society of Hematology ,2008
- Immune synapse formation requires ZAP-70 recruitment by ezrin and CD43 removal by moesinThe Journal of cell biology, 2007
- Tetraspanin CD81 is required for the αvβ5-integrin-dependent particle-binding step of RPE phagocytosisJournal of Cell Science, 2007
- Actin regulation in endocytosisJournal of Cell Science, 2006
- A loss-of-function RNA interference screen for molecular targets in cancerNature, 2006
- Reduced fertility of female mice lacking CD81Developmental Biology, 2005
- Negative Regulation of FcεRI-mediated Degranulation by CD81The Journal of Experimental Medicine, 1997
- Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor: STUDY OF Lck- AND FynT-DEPENDENT T CELL ACTIVATIONJournal of Biological Chemistry, 1996
- Induction of Tyrosine Phosphorylation and Translocation of Ezrin by Hepatocyte Growth Factor/Scatter Factor (HGF/SF)Biochemical and Biophysical Research Communications, 1995