BAI2 mutation associated with a novel neurological disorder

 描述(申请人提供)：BAI2是一种G蛋白偶联受体，几乎只在中枢神经系统中表达。这种受体在星形胶质细胞和某些神经元群体中高度表达。NIH未诊断疾病项目最近发现BAI2突变与一种新的神经疾病有关。这种与疾病相关的BAI2突变是一种错义突变，它改变了受体细胞质羧基末端的一种氨基酸，BAI2的一个区域被认为对控制受体的信号和调节很重要。在这个项目中，我们将评估疾病相关突变对BAI2的运输和信号转导的影响，以便 确定这种突变可能如何导致人类疾病，并获得对携带这种突变的患者的潜在治疗选择的洞察。此外，这些研究还将阐明BAI2的正常功能，从而为从药理上针对这种受体奠定基础，以便使更广泛的患者受益，这些患者表达野生型BAI2，但患有神经或精神障碍，这些疾病可能可以通过调节BAI2的活性来治疗。

 DESCRIPTION (provided by applicant): BAI2 is a G protein-coupled receptor that is expressed almost exclusively in the central nervous system. This receptor is highly expressed in astrocytes as well as in certain neuronal populations. A BAI2 mutation was recently identified by the NIH Undiagnosed Diseases Program as being associated with a novel neurological disorder. This disease-associated BAI2 mutation is a missense mutation that alters an amino acid in the receptor's cytoplasmic carboxyl-terminus, a region of BAI2 that is known to be important for controlling the receptor's signaling and regulation. In this project, we will assess the effects of the disease-associated mutation on the trafficking and signaling of BAI2 in order to determine how this mutation might be causing human disease and also gain insights into potential therapeutic options for patients harboring this mutation. Moreover, these studies will also shed significant light on the normal function of BAI2 and thereby set the stage for targeting this receptor pharmacologically in order to benefit the wider population of patients who express wild-type BAI2 but suffer from neurological or psychiatric disorders that might be treatable via modulation of BAI2 activity.