Importance of Small GTPases in Photoreceptor Function

小 GTP 酶在感光器功能中的重要性

基本信息

批准号：
9893876
负责人：
Visvanathan Ramamurthy
金额：
$ 35.37万
依托单位：
WEST VIRGINIA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9893876
关键词：
ARL2 gene ARL3 gene Address Adult Affect Animal Model Binding Binding Proteins Biochemical Biological Assay Blindness Cell Culture Techniques Cell Transplantation Cells Characteristics Cilia Clinical Complex Defect Development Disease Embryo Fibroblasts Functional disorder GTP Binding Gene Transfer Genes Goals Growth Growth Factor Guanine Nucleotide Exchange Factors Guanosine Triphosphate Guanosine Triphosphate Phosphohydrolases Human Hydrolysis Impairment In Vitro Inherited Intervention Knock-out Knockout Mice Knowledge Lead Length Light Link Maintenance Microtubule Polymerization Modeling Molecular Monomeric GTP-Binding Proteins Morphogenesis Morphology Mus Mutation Nature Organ Patients Pharmacology Phenotype Photoreceptors Process Protein Family Proteins Regulation Research Retinal Degeneration Retinal Diseases Role Set protein Situs Inversus Structure Syndrome System Tamoxifen Testing Therapeutic Tissue Transplantation Transducin Ursidae Family Vision conditional knockout in vitro Assay mouse model mutant novel therapeutics phosphoric diester hydrolase programs protein function protein transport trafficking treatment strategy

项目摘要

PROJECT SUMMARY/ABSTRACT The long term goals of our research are to identify mechanisms that contribute to the formation and maintenance of photoreceptor outer segments. The goal of this proposal is to explore the regulation of small GTPases that belong to the ARF-like family of proteins and their effect on early development of cilia and photoreceptor outer segment morphogenesis. Interestingly, mutations in small GTPases and their regulators are linked to blindness and syndromic diseases. Our study will also focus on the need for small GTPases in protein trafficking and will test if these GTPases are needed in adult photoreceptors. We will use a combination of unique animal models, cell culture models and in vitro biochemical analyses to comprehensively address the requirement for GTPases and their regulation in ciliated cells including photoreceptors. Our proposed studies are aligned with the Retinal Diseases Program of the NEI to “Identify the genes involved in both inherited and retinal degenerative diseases (including RP), determine the pathophysiological mechanisms underlying these mutations, and determine new potential therapeutic strategies for treatment such as gene transfer, tissue and cell transplantation, growth factor therapy, and pharmacological intervention”. Our proposed studies have clinical implications, such as therapy for mutations in small GTPases that lead to blindness, and which are not currently available.

项目概要/摘要我们研究的长期目标是确定有助于形成和该提案的目标是探索小光感受器外节的调节。属于 ARF 样蛋白家族的 GTP 酶及其对纤毛和纤毛早期发育的影响光感受器外节形态发生、小 GTP 酶及其调节因子的突变。与失明和综合症疾病有关。我们的研究还将重点关注小 GTP 酶的需求。蛋白质运输，并将测试成人光感受器是否需要这些 GTP 酶。结合独特的动物模型、细胞培养模型和体外生化分析全面解决 GTP 酶的需求及其在纤毛细胞中的调节，包括光感受器。我们提出的研究与 NEI 的视网膜疾病计划一致，旨在“识别涉及的基因在遗传性和视网膜退行性疾病（包括 RP）中，确定病理生理学这些突变的机制，并确定新的潜在治疗策略例如基因转移、组织和细胞移植、生长因子治疗等 “药物干预”。我们提出的研究具有临床意义，例如突变治疗。导致失明的小 GTP 酶，目前尚无法获得。