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大鼠视网膜中GABAB受体的结构。

Structure of GABAB receptors in rat retina.

作者信息

Benke Dietmar, Michel Claudia, Mohler Hanns

机构信息

Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

出版信息

J Recept Signal Transduct Res. 2002 Feb-Nov;22(1-4):253-66. doi: 10.1081/rrs-120014600.

Abstract

In the search for yet unknown subtypes of GABAB receptors, the subunit architecture of GABAB receptors in the retina was analyzed using selective antisera. Immunopurification of the splice variants GABAB1a and GABAB1b demonstrated that both were associated with GABAB2. Quantitative immunoprecipitation experiments indicated that practical the entire GABAB receptor population in the retina consists of the receptor subtypes GABAB1a/GABAB2 and GABAB1b/GABAB2, although low levels of GABAB1c/GABAB2 cannot be excluded. The data rule out the existence of GABAB receptors containing the splice variants GABAB1d and GABAB1e. Moreover, no evidence for homomeric GABAB1 receptors was found. Among the splice variants, GABAB1a is by far the predominant one in neonatal and adult retina, whereas GABAB1b is expressed only late in postnatal development and in the adult retina. Since GABAB1a is expressed at high levels before functional synapses are formed, this specific receptor subtype might be involved in the maturation of the retina. Finally, subcellular fractionation demonstrated that GABAB1a, but not GABAB1b, is present in postsynaptic densities, suggesting a differential pre- and postsynaptic localisation of both splice variants.

摘要

为了寻找尚未明确的GABAB受体亚型,我们使用选择性抗血清分析了视网膜中GABAB受体的亚基结构。对剪接变体GABAB1a和GABAB1b进行免疫纯化表明,两者均与GABAB2相关联。定量免疫沉淀实验表明,视网膜中几乎所有的GABAB受体群体均由受体亚型GABAB1a/GABAB2和GABAB1b/GABAB2组成,尽管不能排除低水平的GABAB1c/GABAB2的存在。这些数据排除了含有剪接变体GABAB1d和GABAB1e的GABAB受体的存在。此外,未发现同聚体GABAB1受体的证据。在剪接变体中,GABAB1a在新生和成年视网膜中是迄今为止占主导地位的变体,而GABAB1b仅在出生后发育后期和成年视网膜中表达。由于GABAB1a在功能性突触形成之前就高水平表达,这种特定的受体亚型可能参与了视网膜的成熟过程。最后,亚细胞分级分离表明,GABAB1a存在于突触后致密物中,而GABAB1b则不存在,这表明两种剪接变体在突触前和突触后的定位存在差异。

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