title: Engagement of CD81 induces ezrin tyrosine phosphorylation and its cellular redistribution with filamentous actin.
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.
authors: Stanford University, School of Medicine, Division of Oncology, Stanford, CA 94305, USA.
authors: Greg P
authors: GP
authors: Coffey
authors: Ranjani
authors: R
authors: Rajapaksa
authors: Raymond
authors: R
authors: Liu
authors: Orr
authors: O
authors: Sharpe
authors: Chiung-Chi
authors: CC
authors: Kuo
authors: Sharon Wald
authors: SW
authors: Krauss
authors: Yael
authors: Y
authors: Sagi
authors: R Eric
authors: RE
authors: Davis
authors: Louis M
authors: LM
authors: Staudt
authors: Jeff P
authors: JP
authors: Sharman
authors: William H
authors: WH
authors: Robinson
authors: Shoshana
authors: S
authors: Levy
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000072377:Syk Kinase; D060225:Tetraspanin 28; D014443:Tyrosine / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D015703:Antigens, CD; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; D060225:Tetraspanin 28; D014443:Tyrosine; D000099149:Ezrin; C554798:CD81 protein, human; C000606896:SYK protein, human