Membrane localization, Caveolin-3 association and rapid actions of vitamin D receptor in cardiac myocytes.
The active form of vitamin D, 1alpha, 25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), 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)(2)D(3) treated cardiac myocytes. A 1nM 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)(2)D(3) signal transduction in heart cells and provides further evidence that VDR plays a role in regulation of heart structure and function.
Zhao
Guisheng
G
Department of Pharmacology, University of Michigan, School of Medicine, Ann Arbor, MI 48109, USA.
Simpson
Robert U
RU
D000818:Animals; D051244:Caveolin 3 / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives / Q000494:pharmacology
D051244:Caveolin 3; D018167:Receptors, Calcitriol; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D