MOLECULAR BIOLOGY OF RETINA--SPECIFIC GABA RECEPTORS

描述（改编自申请人的摘要）：GABA在视网膜中的作用是 由GABA-A、GABA-B和GABA-C受体介导。 虽然GABA-A和GABA-C 受体共享某些特征，GABA-C受体具有更长的 和敏感的反应GABA和显示药理学概况 激动剂和拮抗剂，不同于其他GABA受体。 在 此外，GABA-C受体似乎是视网膜特异性的， 由两极和水平细胞组成。 GABA-C的分子组成 受体存在争议。 此前，申请人的实验室已 从牛视网膜中克隆了两个新的GABA受体亚基rho 1和rho 2， 并发现它们与GABA-A受体的结构相似。 有趣的是，rho 1和rho 2在非洲爪蟾卵母细胞中的表达导致了 同源寡聚受体，其电生理特性类似于 GABA C受体。 由于rho亚基在视网膜细胞中表达， 显示GABA-C特性，GABA-C可能由rho亚基组成。 表达GABA-C的双极细胞还含有GABA-A和甘氨酸受体。 因此，GABA-C受体可能是不同亚基的混合物， 受体的种类。 本提案的目标是确定 rho亚基在哺乳动物视网膜GABA-C的形成中起作用 受体。 申请人将使用分子方法来检查 亚基组合产生的受体具有与 体内鉴定的GABA-C受体。 这些信息将引导搜索 对于指定亚基组装成GABA-C的氨基酸序列， 受体。 最后，申请人将测试特定的子单元 通过牛视网膜的免疫沉淀在体内检测组合。

DESCRIPTION (Adapted from applicant's abstract): GABA action in retina is mediated by GABA-A, GABA-B and GABA-C receptors. Although GABA-A and GABA-C receptors share certain features, the GABA-C receptors have a more prolonged and sensitive response to GABA and display a pharmacological profile of agonists and antagonists that is distinct from the other GABA receptors. In addition, GABA-C receptors appear to be retina-specific, and are expressed by bipolars and horizontal cells. The molecular composition of GABA-C receptors is controversial. Previously, the applicant's laboratory has cloned two novel GABA receptor subunits, rho1 and rho2, from bovine retina and found them to have structural similarity to the GABA-A receptor. Interestingly, expression of rho1 and rho2 in Xenopus oocytes results in homo-oligomeric receptors with electrophysiological properties similar to GABA-C receptors. Since rho subunits are expressed in retinal cells that exhibit GABA-C properties, GABA-C could be made up of rho subunits. Bipolars that express GABA-C also contain GABA-A and glycine receptors. Therefore, GABA-C receptors could be a mixture of subunits from different classes of receptors. The goal of this proposal is to determine the role the rho subunits play in the formation of mammalian retinal GABA-C receptors. The applicant will use a molecular approach to examine which subunit combinations create receptors with properties matching those of GABA-C receptors identified in vivo. This information will guide a search for amino acid sequences that specify assembly of subunits into GABA-C receptors. Finally, the applicant will test for specific subunit combinations in vivo by immunoprecipitation of bovine retina.