Cardiac striatin interacts with caveolin-3 and calmodulin in a calcium sensitive manner and regulates cardiomyocyte spontaneous contraction rate

Can J Physiol Pharmacol. 2017 Oct;95(10):1306-1312. doi: 10.1139/cjpp-2017-0155. Epub 2017 Aug 19.

Abstract

Impaired cardiomyocyte contraction rate is detrimental to cardiac function and often lethal. Despite advancements in the field, there is a paucity of information regarding the coordination of molecules implicated in regulating the heart rate. Striatin (STRN) is a dynamic protein with binding domains to calmodulin (CaM) and caveolin (Cav), both of which are regulators of myocardial function. However, its role in cardiomyocyte contraction is not yet determined. Herein, we show that STRN is expressed in cardiomyocytes and is more abundant in atrial myocardium than in ventricles. Cardiac expression of STRN (protein and mRNA) was developmentally regulated with the highest expression being at neonatal stage (day one) and the lowest in adult rats (13 weeks). CaM pulldown assay indicated that the interaction of cardiac STRN with CaM and caveolin-3 (Cav-3) was calcium sensitive. Interestingly, the overexpression of STRN induced an increase (∼2-fold) in the rate of the spontaneous contraction of cultured cardiomyocytes, while the knockdown of STRN reduced their contraction rate (∼40%). The expression level of STRN was inversely proportional to the interaction of Cav-3 with the CaM/STRN complex. Collectively, our data delineate a novel role for STRN in regulating cardiomyocyte spontaneous contraction rate and the dynamics of the STRN/Cav-3/CaM complex.

Keywords: calmodulin; calmoduline; cardiomyocyte; caveolin-3; cavéoline-3; contraction rate; degré de contraction; striatin; striatine.

MeSH terms

  • Age Factors
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling*
  • Calmodulin / metabolism*
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Caveolin 3 / metabolism*
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Myocardial Contraction*
  • Myocytes, Cardiac / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • RNA Interference
  • Rats
  • Time Factors
  • Transfection

Substances

  • Calmodulin
  • Calmodulin-Binding Proteins
  • Cav3 protein, rat
  • Caveolin 3
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Strn protein, rat
  • Calcium