SIGNALING MECHANISMS OF RETINAL BIPOLAR CELLS

视网膜双极细胞的信号传导机制

• 批准号: 8173305
• 负责人: Brett G Jeffrey
• 金额: $ 7.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173305
• 关键词: Cations; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupled; Cyclic GMP; Dendrites; Electroretinography; Event; Funding; GTP-Binding Proteins; Genes; Glutamates; Go Alpha Subunit; Grant; Guanosine Triphosphate; Hydrolysis; Institution; Kinetics; Light; Mediating; Membrane; Metabotropic Glutamate Receptors; Mutation; Photoreceptors; Process; Proteins; RGS Proteins; Recovery; Research; Research Personnel; Resources; Retinal; Rhodopsin; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Source; Transducin; United States National Institutes of Health; Vision; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The signaling pathway in retinal ON-bipolar originates with a unique metabotropic glutamate receptor, mGluR6, which is found exclusively on the dendrites of ON-bipolar cells (ON-BPCs). Via the G-protein GO, mGluR6 is coupled to the activity of an unidentified cation channel such that the light-induced decrease in glutamate causes an increase in channel activity and concomitant membrane depolarization. This sequence of events resembles the well studied signal transduction pathway of photoreceptor outer segments, in which photoexcitation of rhodopsin is coupled via the G-protein, transducin, to the closure of a cGMP-gated cation channel. In the outer segment, the kinetics of the light response is largely determined by the lifetime of activated transducin. In G-protein mediated responses, the rate-limiting step in the termination of the response is usually the hydrolysis of GTP by the G protein ¿ subunit. The hydrolytic process is accelerated by interaction with regulator of G-protein signaling (RGS) proteins. In photoreceptor outer segments, the light response is terminated by rapid deactivation of transducin by the G¿5-RGS9-R9AP complex, and mutations in the genes encoding these proteins severely impair vision by slowing recovery after light flashes. We have identified two similar complexes, G¿5-RGS7 and G¿5-RGS11 in ON-BPC dendrites. We have shown that R9AP is required for stable expression of G¿5-RGS11 in ON-bipolar cell dendrites. Furthermore, using the electroretinogram, we found that the G¿5-RGS11R9AP complex accelerates the initial ON-bipolar cell response to light.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 视网膜ON-双极中的信号传导途径起源于独特的代谢型谷氨酸受体mGluR 6，其仅在ON-双极细胞（ON-BPC）的树突上发现。通过G蛋白GO，mGluR 6与未鉴定的阳离子通道的活性偶联，使得谷氨酸的光诱导减少引起通道活性增加和伴随的膜去极化。该事件序列类似于光感受器外节的充分研究的信号转导途径，其中视紫红质的光激发通过G蛋白转导素偶联到cGMP门控阳离子通道的关闭。在外段中，光响应的动力学在很大程度上取决于激活的转导蛋白的寿命。在G蛋白介导的反应中，反应终止的限速步骤通常是G蛋白亚基对GTP的水解。水解过程通过与G-蛋白信号传导（RGS）蛋白的调节剂相互作用而加速。在光感受器外节中，光反应通过G5-RGS 9-R9 AP复合物快速失活转导蛋白而终止，编码这些蛋白质的基因突变通过在闪光后缓慢恢复而严重损害视力。我们已经在ON-BPC树突中鉴定出两种类似的复合物，G <$5-RGS 7和G <$5-RGS 11。 我们已经表明，R9 AP是在ON-双极细胞树突中稳定表达G <$5-RGS 11所必需的。此外，使用视网膜电图，我们发现G <$5-RGS 11R9 AP复合物加速初始ON双极细胞对光的响应。