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转导的一个结点。此外，Z-Disc已经成为遗传性心脏病和肌营养不良症的“热点”，因为在许多ZDisc蛋白中发现了原因突变。为了鉴定新的Z-Disc蛋白，我们之前已经描述了Calsarcins，一种新的横纹肌特异性蛋白家族。最近，我们还发现了另一种新的170 kDa ZDisc蛋白CEFIP(心脏富含FHL-2相互作用蛋白)，它直接与微丝蛋白FHL-2相互作用，参与细胞内信号转导和心肌肥大的发病。本研究的目的是通过体外和体内实验，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。

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.