Grant: Discovery Grants Program - Individual

Calcium ion cycling determines heart function and heart muscle cell survival/death. The calcium cycling is regulated by calcium release unit of sarcoplasmic reticulum. This unit keeps calcium cycling properly, a process important for heart contract and relaxation. However, the nature of calcium release unit homeostasis has not been fully understood in heart muscle cells. This study is proposed to investigate how a structural protein called ""junctophilin-2"" maintains the normality of calcium release unit in heart muscle cells. Specifically, we will examine how junctophilin-2 protects another protein called junctin in heart muscle cells. Junctin is an important component of calcium release unit. Without junctin, calcium release unit does not work properly and increases calcium ion release from sarcoplasmic reticulum, leading to perturbation of calcium homeostasis in cardiomyocytes. Dysregulation of calcium cycling damages heart function. Thus, we will also examine whether protection of junctin is a mechanisms by which junctophilin-2 keeps calcium release unit working properly. This study will provide molecular basis for junctophilin-2 regulation of junctin in calcium release unit and its influence on calcium cycling. Thus, our findings will significantly increase our understanding of the nature of calcium cycling, which is critical for elucidating mechanistic insights in the biological and pathophysiological states of the heart.