Molecular basis of junctophilin-2 regulation of ryanodine receptor-2 in cardiomyocytes

钙离子循环决定心脏功能和心肌细胞存活/死亡。肌浆网的钙释放单位调节钙循环。这个单位保持钙循环正常，这是心脏收缩和放松的重要过程。然而，在心肌细胞中，钙释放单位稳态的性质尚未完全了解。本研究拟探讨一种名为“junctophilin-2”的结构蛋白如何维持心肌细胞钙释放单位的正常性。具体来说，我们将研究如何junctophilin-2保护另一种蛋白质称为“连接”在心肌细胞。连接蛋白是钙释放单位的重要组成部分。没有连接蛋白，钙释放单位不能正常工作，增加肌浆网钙离子释放，导致心肌细胞钙稳态紊乱。钙循环失调损害心脏功能。因此，我们还将研究连接蛋白的保护是否是一种机制，通过这种机制，连接蛋白-2保持钙释放单位正常工作。本研究将为研究junctophilin-2对钙释放单位中连接蛋白的调节及其对钙循环的影响提供分子基础。因此，我们的研究结果将显着增加我们对钙循环性质的理解，这对于阐明心脏生物学和病理生理学状态的机制见解至关重要。

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.***