Role of CEFIP, a Novel Z-disc Protein, in Cardiac Hypertrophy and Cardiomyopathy

肌节Z盘最近被认为是心肌细胞功能和信号传导的节点。此外，Z盘已经成为遗传性心肌病和肌营养不良症的“热点”，因为在许多Zdisc蛋白中发现了因果突变。在努力确定新的Z盘蛋白，我们以前描述了calsarcins，一个新的家庭横纹肌特异性蛋白。最近，我们还发现了CEFIP（心脏富集的FHL-2相互作用蛋白），另一种新的170 kDa Zdisc蛋白，它直接与肌联蛋白和细丝蛋白结合蛋白FHL-2相互作用，已知参与细胞内信号转导和心肌肥大的发病机制。目前的建议的目的是进一步阐明CEFIP的分子功能及其在心肌病发病机制中的潜在作用，利用体外和体内实验。

The sarcomeric Z-disc has recently been recognized as a nodal point in cardiomyocyte function and signalling. Moreover, the Z-disc has emerged as a “hot spot” for inherited cardioyopathies and muscular dystrophy, as causal mutations have been found in numerous Zdisc proteins. In an effort to identify novel Z-disc proteins we have previously described the calsarcins, a new family of striated muscle-specific proteins. Recently, we have also discovered CEFIP (Cardiac-enriched FHL-2 interacting protein), another novel 170 kDa Zdisc protein, which directly interacts with the titin- and filamin-binding protein FHL-2, known to be involved in intracellular signal transduction and in the pathogenesis of cardiac hypertrophy. The aim of the current proposal is to further elucidate the molecular functions of CEFIP and its potential role in the pathogenesis of cardiomyopathy, utilizing both in vitro as well as in vivo experiments.