Calpain regulation of integrin IIb 3 signaling in human platelets

• Published in: Platelets (Edinburgh) 2000, Vol.11 (4), p.189-198
• Main Author: M. Schoenwaelder, Yuping Yuan, Shaun P. Jackson, Simone
• Format: Article
• Language: English
• ISSN: 0953-7104; 1369-1635
• DOI: 10.1080/09537100050057620

Efficient platelet adhesion and aggregation at sites of vascular injury requires the synergistic contribution of multiple adhesion receptors. The initial adhesion of platelets to subendothelial matrix proteins involves GPIb/ V/IX and one or more platelet integrins, including integrin αIIb β3 , α2 β1 , α5 β1 and possibly α6 β1. In contrast, platelet-platelet adhesion (platelet cohesion or aggregation) is mediated exclusively by GPIb/V/IX and integrin αIIb β3 . Integrin αIIb β3 is a remarkable receptor that not only stabilizes platelet-vessel wall and platelet-platelet adhesion contacts, but also transduces signals necessary for a range of other functional responses. These signals are linked to cytoskeletal reorganization and platelet spreading, membrane vesiculation and fibrin clot formation, and tension development on a fibrin clot leading to clot retraction. This diverse functional role of integrin αIIb β3 is reflected by its ability to induce the activation of a broad range of signaling enzymes that are involved in membrane phospholipid metabolism, protein phosphorylation, calcium mobilization and activation of small GTPases. An important calcium-dependent signaling enzyme involved in integrin αIIb β3 outside-in signaling is the thiol protease, calpain. This enzyme proteolyses a number of key structural and signaling proteins involved in cytoskeletal remodeling and platelet activation. These proteolytic events appear to play a potentially important role in modulating the adhesive and signaling function of integrin αIIb β3 .