The functions of PDZ domain scaffold proteins in Usher syndrome

描述(申请人提供)：人类亚瑟综合征是最常见的耳聋致盲原因，其特征是先天性耳聋，原因是感觉性毛细胞丧失，以及进行性视网膜变性，原因是视网膜色素变性。12个不同的染色体位点与亚瑟综合征有关，到目前为止，已确定其中9个基因。识别缺失的Usher基因对于诊断和患者咨询至关重要。这九个已知基因编码的不同类型的蛋白质范围之广令人惊讶。尽管人们对这些蛋白质的作用知之甚少，但最近的研究表明，它们在一个多分子复合体中共同发挥作用。本项目重点分析在组织复合体中发挥核心作用的两种支架蛋白，以及这种组织支架的一个新的潜在成员。该项目有三个主要目标：1)确定新发现的基因是否编码Usher支架蛋白，2)分析支架蛋白在将Usher蛋白组织成复合体方面的功能，以及3)确定Usher蛋白复合体在内耳和视网膜细胞中的功能。

DESCRIPTION (provided by applicant): Human Usher syndrome, the most frequent cause of deaf blindness, is characterized by congenital deafness, due to loss of sensory hair cells, and progressive retinal degeneration, due to retinitis pigmentosa. Twelve different chromosomal loci have been linked to Usher syndrome and nine of the genes have been identified to date. Identification of the missing Usher genes is crucial for diagnosis and patient counseling. The nine known genes encode a surprisingly broad range of different types of proteins. Although the roles of these proteins are poorly understood, recent studies suggest that they function together in a multimolecular complex. This project focuses on analysis of the two scaffold proteins that play a central role in organizing the complex, and a new potential member of this organizing scaffold. The project has three main aims: 1) to determine whether the newly discovered gene encodes an Usher scaffold protein, 2) to analyze the functions of the scaffold proteins in organizing the Usher proteins into a complex, and 3) to determine how the Usher protein complex functions in cells of the inner ear and retina.