Martínez-Torres A, Vazquez A E, Panicker M M, Miledi R
Department of Psychobiology, Laboratory of Cellular and Molecular Neurobiology, University of California at Irvine, Irvine, CA 92697-4550, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):4019-22. doi: 10.1073/pnas.95.7.4019.
The rho1 gamma-aminobutyrate receptor (GABArho1) is expressed predominantly in the retina and forms homomeric GABA-gated Cl- channels that are clearly different from the multisubunit GABAA receptors. In contrast to these, GABArho1 receptors desensitize very little and are not blocked by bicuculline. In addition to GABArho1, two new variants were identified in human retina cDNA libraries. Cloning and sequence analysis showed that both variants contain large deletions in the putative extracellular domain of the receptor. These deletions extend from a common 5' site to different 3' sites. The cDNA with the largest deletion, named GABArho1Delta450, contains a complete ORF identical to that of GABArho1 but missing 450 nt. This cDNA encodes a protein of 323 aa, identical to the GABArho1, but has a deletion of 150 aa in the amino-terminal extracellular domain. GABArho1Delta450 mRNA injected into Xenopus oocytes did not produce functional GABA receptors. The second GABArho1 variant (GABArho1Delta51) contains a 51-nt deletion. In Xenopus oocytes, GABArho1Delta51 led to the expression of GABA receptors that had the essential GABArho1 characteristics of low desensitization and bicuculline resistance. Therefore, alternative splicing increases the coding potential of this gene family expressed in the human retina, but the functional diversity created by the alternative spliced forms is still not understood.
rho1γ-氨基丁酸受体（GABArho1）主要在视网膜中表达，并形成同聚体GABA门控氯离子通道，这些通道与多亚基GABAA受体明显不同。与后者相反，GABArho1受体很少脱敏，且不受荷包牡丹碱阻断。除了GABArho1，在人类视网膜cDNA文库中还鉴定出两个新变体。克隆和序列分析表明，这两个变体在受体假定的细胞外结构域中都有大片段缺失。这些缺失从一个共同的5'位点延伸到不同的3'位点。缺失最大的cDNA，命名为GABArho1Delta450，包含一个与GABArho1相同的完整开放阅读框，但缺失450个核苷酸。该cDNA编码一个323个氨基酸的蛋白质，与GABArho1相同，但在氨基末端细胞外结构域有150个氨基酸的缺失。注射到非洲爪蟾卵母细胞中的GABArho1Delta450 mRNA未产生功能性GABA受体。第二个GABArho1变体（GABArho1Delta51）包含一个51个核苷酸的缺失。在非洲爪蟾卵母细胞中，GABArho1Delta51导致表达具有低脱敏和荷包牡丹碱抗性等GABArho1基本特征的GABA受体。因此，可变剪接增加了在人类视网膜中表达的这个基因家族的编码潜力，但由可变剪接形式产生的功能多样性仍不清楚。
