Role of cholesterol in formation and function of a signaling complex involving alpha v beta 3, integrin-associated protein (CD47), and heterotrimericG proteins

Integrin-associated protein (CD47) is a multiply membrane spanning member o f the immunoglobulin superfamily that regulates some adhesion-dependent cel l functions through formation of a complex with alpha v beta 3 integrin and trimeric G proteins. Cholesterol is critical for the association of the th ree protein components of the supramolecular complex and for its signaling. The multiply membrane spanning domain of IAP is required for complex forma tion because it binds cholesterol. The supramolecular complex forms prefere ntially in glycosphingolipid-enriched membrane do-mains. Binding of mAb 10G 2 to the IAP Ig domain, previously shown to be required for association wit h alpha v beta 3, is affected by both the multiply membrane spanning domain and cholesterol. These data demonstrate that cholesterol is an essential c omponent of the alpha v beta 3/IAP/G protein signaling complex, presumably acting through an effect on IAP conformation.