| Abstract: |
Sorcin is a 22-kDa calcium-binding protein initially identified in multidrug-resistant cells; however, its patterns of expression and function in normal tissues are unknown. Here we demonstrate that sorcin is widely 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-kDa ryanodine receptor/calcium release channel recognized by ryanodine receptor-specific antibody. Association of sorcin with a ryanodine receptor complex was confirmed by complementary co-immunoprecipitations of sorcin with the receptor antibody. Forced expression of sorcin in ryanodine 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 transient rise in intracellular calcium in response to caffeine, suggesting organization of the accumulated ryanodine receptor protein into functional calcium release channels. These data demonstrate an interaction between sorcin and the ryanodine receptor and suggest a role for sorcin in modulation of calcium release channel activity, perhaps by stabilizing the channel protein. |
| Keywords: |
immunohistochemistry; controlled study; nonhuman; mouse; animal; mice; animal tissue; cells, cultured; cell line; protein binding; calcium; transfection; mice, inbred balb c; animalia; kinetics; recombinant proteins; lung; fibroblast; phosphoproteins; rats; calcium binding protein; calcium-binding proteins; rodentia; rats, sprague-dawley; calmodulin-binding proteins; heart muscle cell; methionine; calcium cell level; myocardium; cricetinae; cricetulus; cricetulus griseus; caffeine; receptor protein; calcium ion; membrane stabilization; muscle proteins; sarcoplasmic reticulum; microscopy, immunoelectron; calcium channel; calcium channels; male; priority journal; article; calcium binding; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; hamsters; chinese hamster; ryanodine receptor; heart muscle fiber membrane; ryanodine receptor calcium release channel
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