Role of ADAMs in Heart Myocyte Development

描述（由申请人提供）：脊椎动物心脏的发育是 依赖于许多细胞过程，包括迁移，增殖， 分化和凋亡。这些过程的必要条件是相互作用 在相邻细胞之间以及细胞与周围细胞外 矩阵A型去整合素和金属蛋白酶（亚当斯）是近年来发现的一类新的 已鉴定的细胞表面蛋白家族，被认为介导 细胞间相互作用，并在蛋白水解中发挥重要作用， 细胞外基质成分和其它细胞表面分子的裂解。 迄今为止，已经鉴定出至少30种亚当斯，它们的特征都是 多结构域结构，包括金属蛋白酶，去整合素，富含半胱氨酸， 表皮生长因子样、跨膜和胞质结构域。我们有 最近确定心肌细胞表达几种亚当斯; 然而，它们在肌细胞发育中的作用尚未确定。基于 其他系统中已发表的文献和提供的初步数据 在这里，我们假设亚当斯通过其多结构域结构， 在心肌细胞发育和组织中的重要作用。而且我们 假设由亚当斯定位金属蛋白酶活性， ADAM介导的细胞-细胞相互作用对正常心肌细胞至关重要 发展旨在测试这些假设的实验目标包括： 1)以确定特定亚当斯的改变是否影响 心肌细胞的分化、组织或功能; 2）确定 ADAM金属蛋白酶活性在心肌组织中的功能作用 和成熟;和3）确定ADAM介导的细胞-细胞 调节肌细胞发育和组织的相互作用。这些研究 将阐明这种新的蛋白质家族成员的作用， 心肌细胞分化和组织在发育中的心脏。

DESCRIPTION (provided by applicant): Development of the vertebrate heart is dependent on a number of cellular processes including migration, proliferation, differentiation and apoptosis. Imperative to these processes are interactions between adjacent cells and between cells and the surrounding extracellular matrix. The A Disintegrin And Metalloproteases (ADAMs) are a recently identified family of cell surface proteins that are thought to mediate cell-cell interactions and to play significant roles in the proteolytic cleavage of extracellular matrix components and other cell surface molecules. There are at least 30 ADAMs identified to date which are all characterized by a multidomain structure including metalloprotease, disintegrin, cysteine-rich, epidermal growth factor-like, transmembrane and cytoplasmic domains. We have recently determined that several ADAMs are expressed by heart myocytes; however, their roles in myocyte development have not been determined. Based on the published literature in other systems and the preliminary data presented here, we hypothesize that ADAMs, through their multidomain structure, play essential roles in cardiomyocyte development and organization. Furthermore, we hypothesize that localized metalloprotease activity by the ADAMs and ADAM-mediated cell-cell interactions are imperative to normal myocyte development. The experimental aims designed to test these hypotheses include: 1) to determine whether alterations in expression of specific ADAMs affects the differentiation, organization or function of heart myocytes; 2) to determine the functional roles of ADAM metalloprotease activity in myocyte organization and maturation; and 3) to determine the roles of ADAM-mediated cell-cell interactions in modulating myocyte development and organization. These studies will elucidate the roles of members of this novel protein family in cardiomyocyte differentiation and organization in the developing heart.