© 2000 American Heart Association, Inc.
Cellular Biology |
Dystrophin Associates With Caveolae of Rat Cardiac Myocytes
Relationship to Dystroglycan
From the Departments of Medicine (E.P.) and Neurobiology, Pharmacology and Physiology (D.D.D., G.G., J.U.-E., S.K.A., A.M., H.C.P., E.P.), University of Chicago, Chicago, Ill. G.G.’s present address is Children’s Memorial Institute for Education and Research, Chicago, Ill. S.K.A.’s present address is Cardiology Section, Denver Health Medical Center, Denver, Colo.
Correspondence to Ernest Page, Department of Medicine MC5085, 5841 S Maryland Ave, Chicago, IL 60637. E-mail page{at}hearts.bsd.uchicago.edu
Abstract—The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3–enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found to contain dystrophin and dystroglycan. Further purification of cav-3–containing membranes by immunoprecipitation using anti–cav-3–coated magnetic beads yielded dystrophin but not always dystroglycan. Electron microscopic analysis of precipitated material revealed caveola-sized vesicular profiles that could be double-labeled with anti-dystrophin and anti–cav-3 antibodies. In contrast, immunoprecipitation of membranes with anti-dystrophin–coated beads yielded both cav-3 and dystroglycan. Electron microscopic analysis of this material showed heterogeneous membrane profiles, some of which could be decorated with anti–cav-3 antibodies. To confirm that dystrophin and cav-3 were closely associated in cardiac myocytes, we verified that dystrophin was also present in immunoprecipitated cav-3–containing membranes from detergent extracts, as well as in sonicated extracts of purified ventricular myocytes. Confocal immunofluorescence microscopy of ventricular and atrial cardiac myocytes showed that the cellular distributions of cav-3 and dystrophin partially overlapped. Immuno–electron micrographs of thin sections of rat atrial myocytes revealed a fraction of dystrophin molecules that are in apparently close apposition to caveolae. These results suggest that a subpopulation of dystrophin molecules interacts with cardiac myocyte caveolae in vivo and that some of the dystrophin is engaged in linking cav-3 with the dystroglycan complex.
Key Words: heart • myocyte • caveolae • dystrophin
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