Striatin is a novel regulator of calcium homeostasis in cardiomyocytes

Abstract

Striatin is a scaffold protein that associates with caveolin and calmodulin; key regulators of excitation‐contraction coupling in the heart. The aim of the present study was to probe for a potential role for striatin in regulating calcium homeostasis in cardiomyocytes. Our findings indicate that striatin is expressed in rat hearts (cardiomyocytes enriched fraction) with a higher expression level in neonates vs adults. Protein‐protein interaction assays revealed that, in the heart, striatin associates with calmodulin as well as caveolin‐1 and caveolin‐3 (muscle specific isoform). It was notable that the interaction between striatin and calmodulin was calcium sensitive: while calcium chloride (2 mM) showed robust pulldown of striatin with calmodulin, the calcium chelator EGTA (1 mM) attenuated this interaction. Moreover, KCl‐induced intracellular calcium [Ca2+]i increase was sustained in cardiomyocytes overexpressing striatin (adenoviral delivery) while [Ca2+]i returned to near basal levels in control cardiomyocytes (non‐target adenovirus). Collectively, our data indicate that striatin is expressed in cardiomyocytes and that it may play a role in maintaining [Ca2+]i homeostasis. This suggests that striatin may be involved in modulating cardiac excitation‐contraction coupling and emerges as a novel target for therapeutic strategies in cardiac diseases.