BAI2 mutation associated with a novel neurological disorder

BAI2 突变与新型神经系统疾病相关

• 批准号: 8877775
• 负责人: Randy A. Hall
• 金额: $ 19.5万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8877775
• 关键词: Actins; Affect; Amino Acids; Arginine; Astrocytes; Atrophic; BAI2 gene; Binding Proteins; Biological Assay; Biology; Brain; Cell Survival; Cell membrane; Coupled; Coupling; Cyclic AMP; Cytoplasmic Protein; Cytoplasmic Receptors; Cytoskeleton; Development; Disease; Endoplasmic Reticulum; Environment; Evoked Potentials; Evolution; Excision; Exhibits; Family; Future; G-Protein-Coupled Receptors; GTP-Binding Proteins; Gene Mutation; Genes; Genetic; Human; Induced Mutation; Knockout Mice; Length; Ligands; Light; Luciferases; Mediating; Mental disorders; Missense Mutation; Mus; Mutation; Neuraxis; Neurons; Pathology; Patients; Phenotype; Play; Population; Production; Property; Proteins; Quadripareses; Reagent; Receptor Signaling; Regulation; Relative (related person); Reporting; Role; Sensory; Signal Transduction; Spastic; Spinal Cord; Staging; Testing; Therapeutic; Toxic effect; Transcriptional Regulation; Tryptophan; United States National Institutes of Health; cell motility; extracellular; gain of function; genetic variant; human disease; in vivo; insight; member; nervous system disorder; neurological pathology; novel; patient population; programs; protein folding; public health relevance; receptor; small molecule; trafficking

 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.

 描述（由申请人提供）：BAI 2是一种G蛋白偶联受体，几乎仅在中枢神经系统中表达。该受体在星形胶质细胞以及某些神经元群体中高度表达。NIH未诊断疾病项目最近发现了一种BAI2突变，与一种新的神经系统疾病有关。这种疾病相关的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个氨基酸，这是已知对控制受体信号传导和调节很重要的BAI2区域。在这个项目中，我们将评估疾病相关突变对BAI 2的运输和信号传导的影响，以便 确定这种突变如何导致人类疾病，并深入了解携带这种突变的患者的潜在治疗方案。此外，这些研究还将揭示BAI 2的正常功能，从而为靶向这种受体的研究奠定基础，以使更广泛的表达野生型BAI 2但患有神经系统或精神疾病的患者群体受益，这些患者可能通过调节BAI 2活性来治疗。