Membrane localization,Caveolin-3 association and rapid actions of vitamin D receptor in cardiac myocytes |
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| Authors: | Guisheng Zhao Robert U Simpson |
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| Institution: | 1. Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China;2. Cadet Brigade, Third Military Medical University, Chongqing 400038, China;1. Department of Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand;2. Faculty of Agriculture and Life Sciences, Lincoln University, Canterbury, New Zealand;1. Department of Critical Care Medicine, Mayo Clinic, 5777 East Mayo Boulevard, Phoenix, AZ 85054, USA;2. Division of Cardiovascular Diseases, Mayo Clinic, Phoenix, AZ, USA;1. Division of Aging, Department of Medicine, Brigham and Women''s Hospital, Boston, Massachusetts;2. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota;3. Massachusetts Veterans Epidemiology and Research Information Center and Geriatric Research, Boston, Massachusetts;4. Division of Preventive Medicine, Brigham and Women''s Hospital, Boston, Massachusetts;1. Department of Obstetrics and Gynecology, The First Hospital, Harbin Medical University, Harbin, China;2. Department of Obstetrics and Gynecology, LSUHSC-Shreveport, LA, USA |
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| Abstract: | The active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), mediates both genomic and rapid non-genomic actions in heart cells. We have previously shown that the vitamin D receptor (VDR) is located in the t-tubular structure of cardiomyocytes. Here we show that VDR specifically interacts with Caveolin-3 in the t-tubules and sarcolemma of adult rat cardiac myocytes. Co-immunoprecipitation studies using VDR antibodies revealed that Caveolin-3 specifically co-precipitates with the VDR and similarly the VDR is co-precipitated with Caveolin-3 antibody. Confocal immuno-fluorescence microscopy analysis also showed co-localization of VDR and Caveolin-3 in t-tubules and sarcolemma. The non-genomic effects of the functional VDR were studied in electrically stimulated myocytes isolated from adult rat hearts. Sarcomere shortening and re-lengthening were measured in 1,25(OH)2D3 treated cardiac myocytes. A 1 nM treatment decreased peak shortening within minutes, suggesting a rapid effect through the membrane-bound VDR. This novel finding of the interaction between VDR and Caveolin-3 is fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and provides further evidence that VDR plays a role in regulation of heart structure and function. |
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