ASSOCIATION OF SORCIN WITH THE CARDIAC RYANODINE RECEPTOR

Sorcin is a 22 kDa calcium-binding protein initially identified in mul tidrug-resistant cells; however, its patterns of expression and functi on in normal tissues are unknown. Here we demonstrate that sorcin is w idely distributed in rodent tissues, including the heart, where it was localized by immunoelectron microscopy to the sarcoplasmic reticulum. A > 500-kDa protein band immunoprecipitated from cardiac myocytes by sorcin antiserum was indistinguishable in size on gels from the 565-kD a ryanodine receptor/calcium release channel recognized by ryanodine r eceptor-specific antibody. Association of sorcin with a ryanodine rece ptor complex was confirmed by complementary co-immunoprecipitations of sorcin with the receptor antibody. Forced expression of sorcin in rya nodine receptor-negative Chinese hamster lung fibroblasts resulted in accumulation of the predicted 22-kDa protein as well as the unexpected appearance of ryanodine receptor protein. In contrast to the parental host fibroblasts, sorcin transfectants displayed a rapid and transien t rise in intracellular calcium in response to caffeine, suggesting or ganization of the accumulated ryanodine receptor protein into function al calcium release channels. These data demonstrate an interaction bet ween sorcin and the ryanodine receptor and suggest a role for sorcin i n modulation of calcium release channel activity, perhaps by stabilizi ng the channel protein.