ANALYSIS OF A NOVEL MUSCLE INTEGRIN-BINDING PROTEIN

描述（取自应用程序）： 细胞与细胞外基质的适当相互作用对于 以及肌肉的正常功能。最近的研究表明 整合素胞质结构域在控制肌生成中的重要功能 因此，这意味着整合素和它们的 细胞内配体可能在肌生成中起关键作用。长期 拟议研究的目的是了解分子基础和 整合素细胞内相互作用在肌发生和肌病中的功能。 拟议的研究重点是一种新的肌肉特异性细胞内 整合素结合蛋白（MIBP），最近被鉴定和克隆的 申请人。MIBP在体内和体外与β 1整联蛋白相互作用。更 重要的是，MIBP表达在肌原性生长过程中显著下调， 成肌细胞中MIBP的分化和过表达抑制肌原性 分化拟议的研究将检验以下假设： MIBP与p1整合素的结合调节整合素的功能、成肌细胞增殖 和差异化。提出了具有以下具体目标的实验： (1)为了确定MIBP-整联蛋白相互作用的结构基础， (2)确定MIBP-整合素相互作用是否调节成肌细胞 分化和增殖，和（3）评估的影响， MIBP-整合素相互作用对整合素活化和细胞外基质的影响 证词这些实验的结果将提供分子基础， 未来的全面调查，包括那些在组织和动物 水平以及人类患者。细胞内整合素的研究 肌肉细胞中的相互作用可能会导致对一般 整合素在肌肉发育中的作用机制和 肌肉疾病，并可能转化为新的治疗方法， 控制肌细胞增殖和分化的方法，以及 从而导致肌营养不良症和其他肌病。

DESCRIPTION (Taken from the application): Proper cellular interactions with extracellular matrix are critical for development as well as normal function of muscles. Recent studies have revealed important functions of integrin cytoplasmic domains in control of myogenesis and therefore implied that the interactions between integrin and their intracellular ligands may play a pivotal role in myogenesis. The long term objective of the proposed research is to understand the molecular bases and the functions of integrin intracellular interactions in myogenesis and myopathies. The proposed research focuses on a novel muscle-specific intracellular integrin-binding protein (MIBP) that was recently identified and cloned by the applicant. MIBP interacts with p1 integrin in vivo as well as in vitro. More importantly, MIBP expression is dramatically down-regulated during myogenic differentiation and overexpression of MIBP in myoblasts suppresses myogenic differentiation. The proposed studies will test the hypothesis that the binding of MIBP to the p1 integrin modulates integrin function, myoblast proliferation and differentiation. Experiments with the following specific aims are proposed: (1) To define the structural basis underlying the MIBP-integrin interaction, (2) To determine whether the MIBP-integrin interaction modulates myoblast differentiation and proliferation, and (3) To assess the effect of the MIBP-integrin interaction on integrin activation and extracellular matrix deposition. Results from these experiments will provide a molecular basis for future comprehensive investigations including those at the tissue and animal level as well as in human patients. Studies on integrin intracellular interactions in muscle cells will likely lead to insights into the general mechanism by which integrin function in muscle development and pathogenesis of muscle diseases, and may potentially translate into novel therapeutic approaches to control muscle cell proliferation and differentiation, and consequently, the outcome of muscular dystrophies and other myopathies.