Role of ADAMs in Heart Myocyte Development

ADAM 在心肌细胞发育中的作用

• 批准号: 6758029
• 负责人: WAYNE E CARVER
• 金额: $ 25.29万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758029
• 关键词: cardiac myocytes; cell cell interaction; cell differentiation; cell growth regulation; embryo /fetus culture; laboratory rat; membrane proteins; metalloendopeptidases; newborn animals; platelet aggregation inhibitors; protein structure function; tissue /cell culture

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.

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交互 相邻细胞之间以及细胞与周围细胞外细胞之间 矩阵。 A 解整合素和金属蛋白酶 (ADAM) 是最近 确定了被认为介导的细胞表面蛋白家族 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他细胞表面分子的裂解。 迄今为止，至少已识别出 30 个 ADAM，其特点是 多结构域结构，包括金属蛋白酶、解整合素、富含半胱氨酸、 表皮生长因子样、跨膜和细胞质结构域。我们有 最近确定心肌细胞表达多种 ADAM； 然而，它们在心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 ADAM 通过其多域结构发挥作用 在心肌细胞发育和组织中发挥重要作用。此外，我们 假设 ADAM 的局部金属蛋白酶活性和 ADAM 介导的细胞间相互作用对于正常心肌细胞至关重要 发展。旨在检验这些假设的实验目标包括： 1) 确定特定 ADAM 表达的改变是否会影响 心肌细胞的分化、组织或功能； 2）确定 ADAM 金属蛋白酶活性在肌细胞组织中的功能作用 和成熟； 3) 确定 ADAM 介导的细胞间作用 调节心肌细胞发育和组织中的相互作用。这些研究 将阐明这个新蛋白质家族成员的作用 发育中的心脏中心肌细胞的分化和组织。