Homozygous loss of mouse tetraspanin CD82 enhances integrin [alpha]IIb[beta]3 expression and clot retraction in platelets

Integrin [alpha]IIb[beta]3 is critical for platelet-mediated blood clotting. Tetraspanins are well-established regulators of integrins and genetic loss of tetraspanin CD151 or TSSC6 in mice leads to increased bleeding due to inadequate integrin [alpha]IIb[beta]3 outside-in signaling. Conversely, mild but enhanced integrin [alpha]IIb[beta]3 activation and hyperaggregation is observed in CD9 and CD63 null mice respectively. CD82 is reportedly expressed in platelets; however its function is unknown. Using genetically engineered CD82 null mice, we investigated the role of the tetraspanin CD82 in platelet activation. Loss of CD82 resulted in reduced bleed times in vivo . CD82 was present on the surface of both human and mouse platelets, and its levels did not change upon platelet activation or degranulation. No differences in platelet activation, degranulation, or aggregation in response to ADP or collagen were detected in CD82 null mice. However, the kinetics of clot retraction was enhanced, which was intrinsic to the CD82-null platelets. Integrin [alpha]IIb[beta]3 surface expression was elevated on the platelets from CD82 null mice and they displayed enhanced adhesion and tyrosine kinase signaling on fibrinogen. This is the first report on CD82 function in platelets; which we found intrinsically modulates clot retraction, integrin [alpha]IIb[beta]3 expression, cell adhesion, and tyrosine signaling. * First report on the function of tetraspanin CD82 in platelets. * CD82 knockout in mice reduces bleeding time in vivo. * CD82 loss intrinsically enhances platelet-mediated clot retraction in vitro. * CD82 suppresses integrin [alpha]IIb[beta]3 expression. * CD82 suppresses adhesion and tyrosine kinase signaling on fibrinogen.