Interaction between vitamin D receptor with caveolin-3 and regulation by 1,25-dihydroxyvitamin D3 in adult rat cardiomyocytes.

We show that 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) and a synthetic non-genotropic vitamin D analog agonist, 1a,25(OH)2-lumisterol (JN), exhibit similar rapid effects on sarcomere shortening (contraction) of isolated adult cardiomyocyte. We also report that the vitamin D receptor (VDR) specifically interacts with caveolin-3 in the t-tubules and sarcolemma of isolated adult rat cardiac myocytes. Confocal immunofluorescence microscopy analysis showed co-localization of VDR and caveolin-3 in the t-tubules and sarcolemma of cardiomyocytes. 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. VDR is also in association with Serca-2, the sarcoplasmic reticulum Ca2+-ATPase, as demonstrated by co-immunoprecipitation, suggesting a role of VDR in regulating cardiac contractility by direct interaction with Serca-2. Treatment of isolated adult rat cardiomyocytes with 10 nM 1,25(OH)2D3 for 1 h caused decreased association between VDR and caveolin-3. These discoveries of the association between VDR and caveolin-3 and the regulation of this interaction by 1,25(OH)2D3 are fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and suggest a novel mechanism for VDR in the regulation of heart structure and function.