Association of Sorcin With the Cardiac Ryanodine Receptor (*)
- Marian B. Meyers(1)(§),
- Virginia M. Pickel(2),
- Shey-Shing Sheu(3),
- Virendra K. Sharma(3),
- Kathleen W. Scotto(4) and
- Glenn I. Fishman(1)(¶)
- From the (1) Department of Medicine, Section of Molecular Cardiology, Albert Einstein College of Medicine, Bronx, New York 10461,
- the (2) Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021,
- the (3) Department of Pharmacology, University of Rochester Medical Center, Rochester, New York 14642, and
- the (4) Molecular Pharmacology and Therapeutics Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021
- § To whom correspondence should be addressed: Dept. of Medicine, Div. of Cardiology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Tel: 718-430-2619; Fax: 718-823-0032.
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.
Footnotes
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↵¶ Established Investigator of the American Heart Association.
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↵* This work was supported by a Bristol-Myers Squibb Award (to M. B. M.), Cancer Center Support Grant NCI P30-CA-08748 (to Memorial Sloan-Kettering Cancer Center), National Institutes of Health (NIH) Grant HL-33333 (to S-S. S. and V. K. S.), NIMH Career Award Grant MH-00078, NIMH Grant MH48776, and NIH Grant HL-18974 (to V. M. P.), and NIH Physician Scientist Award HL-02391 (to G. I. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- RyR
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ryanodine receptor
- SR
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sarcoplasmic reticulum.
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- Received May 17, 1995.
- Revision received August 30, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
