The functions of PDZ domain scaffold proteins in Usher syndrome

描述（由申请人提供）：人类Usher综合征是聋盲的最常见原因，其特征是先天性耳聋，由于感觉毛细胞的丧失，以及由于视网膜色素变性导致的进行性视网膜变性。12个不同的染色体位点与Usher综合征有关，其中9个基因已被确定。鉴定缺失的Usher基因对于诊断和患者咨询至关重要。这9个已知基因编码的蛋白质种类之广令人惊讶。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物中共同起作用。该项目侧重于分析在组织复合体中起核心作用的两种支架蛋白，以及这种组织支架的新潜在成员。该项目有三个主要目的：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蛋白组织成复合物中的功能，以及3)确定Usher蛋白复合物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.