Cell-Cell and Cell-ECM Adhesion in Cardiac Function and Disease

细胞粘附分子（CAM）可以介导细胞-细胞和细胞-细胞外基质（ECM）粘附，如 在多细胞生物体中，控制着最基本的性质，包括细胞形态， 迁移、增殖、分化、组织形态发生和胚胎发育。最近的研究 我现在还发现，在编码CAM的基因中发现了突变，并与各种 疾病，包括癌症、自身免疫性疾病以及心肌病 这个提议是为了验证中心假设，即细胞-细胞（即细胞）的心脏成分。斑珠蛋白），和/或 细胞-ECM（即PINCH）粘附复合物在致瘤性右室肥厚的病因学中起重要作用。 心室发育不良/心肌病（ARVD/C）和心脏功能和/或修复。因此，具体 目标是： 具体目标1：了解人类斑珠蛋白突变导致 Naxos病，ARVD/C的一种隐性形式。 具体目标2：确定ARVD/C表型是否由细胞自主要求引起 了解ICD和胞质/核斑珠蛋白在心肌细胞中的作用， 这种疾病。 具体目标3：研究PINCH在心脏发育、损伤和修复中的功能作用。

Cell adhesion molecules (CAMs) can mediate both cell-cell and cell-extracellular matrix (ECM) adhesions, as welt as govern the most fundamental properties within multicellular organisms, including cell morphology, migration, proliferation, differentiation, tissue morphogenesis, and embryonic development. Recent studies have now also revealed that mutations in genes encoding CAMs are found and associated with various diseases, including cancers, autoimmune diseases as well as cardiomyopathies This proposal is to test the central hypothesis that cardiac components of cell-cell (ie. plakoglobin), and/or cell-ECM (ie.PINCH) adhesion complexes play important roles in the etiology of arrhythmogenic right ventricular dysplasia/ cardiomyopathy (ARVD/C) and cardiac function and/or repair. Accordingly, the specific aims are: Specific Aim 1: To understand the molecular mechanism by which the human plakoglobin mutation results in Naxos disease, a recessive form of ARVD/C. Specific Aim 2: To determine whether the ARVD/C phenotype results from a cell autonomous requirement for plakoglobin in cardiomyocytes and to understand the role of ICD and cytoplasmic/nuclear plakoglobin in this disease. Specific Aim 3: To study the functional role of PINCH in cardiac development, injury, and repair.