Physical interaction between calcineurin and Cav3.2 T-type Ca2+ channel modulates their functions

Ca(v)3.2 T-type Ca2+ channel is required for the activation of calcineurin/NFAT signaling in cardiac hypertrophy. We aimed to investigate how Ca(v)3.2 and calcineurin interact. We found that Ca2+ and calmodulin modulate the Ca(v)3.2/calcineurin interaction. Calcineurin binding to Ca(v)3.2 decreases the enzyme's phosphatase activity and diminishes the channel's current density. Phenylephrine-induced hypertrophy in neonatal cardiac myocytes is reduced by a cell-permeable peptide with the calcineurin binding site sequence. These data suggest that Ca(v)3.2 regulates calcineurin/NFAT pathway through both the Ca2+ influx and calcineurin binding. Our findings unveiled a reciprocal regulation of Ca2+ signaling which contributes to our understanding of cardiac hypertrophy. Structured summary of protein interactions: Ca(v)3.2 physically interacts with cn by anti tag coimmunoprecipitation (View interaction) (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.