钙蛋白酶的调节及其失调对闰盘的影响。

Calpain Regulation and Dysregulation-Its Effects on the Intercalated Disk.

机构信息

Biochemistry, Chemistry, Engineering, and Physics Department, Commonwealth University of Pennsylvania, 31 Academy St., Mansfield, PA 16933, USA.

Department of Chemistry and Biochemistry, James Madison University, 901 Carrier Dr., Harrisonburg, VA 22807, USA.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11726. doi: 10.3390/ijms241411726.

DOI:10.3390/ijms241411726

PMID:37511485

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10380737/

Abstract

The intercalated disk is a cardiac specific structure composed of three main protein complexes-adherens junctions, desmosomes, and gap junctions-that work in concert to provide mechanical stability and electrical synchronization to the heart. Each substructure is regulated through a variety of mechanisms including proteolysis. Calpain proteases, a class of cysteine proteases dependent on calcium for activation, have recently emerged as important regulators of individual intercalated disk components. In this review, we will examine how calcium homeostasis regulates normal calpain function. We will also explore how calpains modulate gap junctions, desmosomes, and adherens junctions activity by targeting specific proteins, and describe the molecular mechanisms of how calpain dysregulation leads to structural and signaling defects within the heart. We will then examine how changes in calpain activity affects cardiomyocytes, and how such changes underlie various heart diseases.

摘要

闰盘是一种心脏特异性结构，由三个主要的蛋白质复合物组成——黏附连接、桥粒和缝隙连接，它们协同工作为心脏提供机械稳定性和电同步。每个亚结构都通过多种机制进行调节，包括蛋白水解。钙蛋白酶是一类依赖钙激活的半胱氨酸蛋白酶，最近已成为调节个别闰盘成分的重要调节剂。在这篇综述中，我们将探讨钙稳态如何调节正常钙蛋白酶功能。我们还将探讨钙蛋白酶如何通过靶向特定蛋白质来调节缝隙连接、桥粒和黏附连接的活性，并描述钙蛋白酶失调导致心脏结构和信号缺陷的分子机制。然后，我们将研究钙蛋白酶活性的变化如何影响心肌细胞，以及这种变化如何导致各种心脏疾病。