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γ-氨基丁酸A(GABA(A))受体相关蛋白的三种人类同源物和两种小鼠同源物的克隆、表达模式及染色体定位

Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein.

作者信息

Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S

机构信息

State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.

出版信息

Genomics. 2001 Jun 15;74(3):408-13. doi: 10.1006/geno.2001.6555.

DOI:10.1006/geno.2001.6555
PMID:11414770
Abstract

Type A receptors of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, contain alpha, beta, delta, gamma, and rho subunits. The gamma subunit has four subtypes: gamma1, gamma2, gamma3, andgamma4. GABA(A) receptor-associated protein (GABARAP) was previously demonstrated to act as a linker protein between microtubules and the gamma2 subunit of GABA(A) receptors. However, no other linker proteins have been identified as mediating the linkage of microtubules and the remaining subunits of GABA(A) receptors. In this study we identified three human paralogues (GABARAPL1, GABARAPL2, and GABARAPL3) and two mouse orthologues (Gabarapl1 and Gabarapl2) of human GABARAP, all of which encoded 117 amino acids, as does Gabarapl. The expression patterns of GABARAPL1, GABARAPL2, and GABARAP in 16 adult tissues showed that they were expressed ubiquitously. The expression levels of GABARAPL1 as a 2.3-kb transcript were very high in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle, very low in thymus and small intestine, and moderate in other tissues tested. The unique 1.35-kb transcript of GABARAPL2 was expressed at high levels in heart, brain, testis, prostate, ovary, spleen, and skeletal muscle, at very low levels in lung, thymus, and small intestine, and moderately in other tissues tested. For GABARAP, a 1.3-kb transcript was abundantly expressed in all tested tissues with small variation. The expression patterns of Gabarapl1 and Gabarapl2 were similar to those of their counterparts in human. In addition, GABARAPL1 was localized to human chromosome 12p12.3 and GABARAPL2 to 16q22.3-q24.1 by RH mapping, while GABARAP and GABARAPL3 were found to be localized at chromosomes 17p13.2 and 15q25.1, respectively, by searching the related databases. Sequence comparison of the cDNAs and their corresponding genomic sequences shows that GABARAP, GABARAPL1, and GABARAPL2 are composed of four exons each, while GABARAPL3 is distributed only at one exon.

摘要

γ-氨基丁酸(GABA,一种抑制性神经递质)的A型受体包含α、β、δ、γ和ρ亚基。γ亚基有四种亚型:γ1、γ2、γ3和γ4。GABA(A)受体相关蛋白(GABARAP)先前被证明可作为微管与GABA(A)受体γ2亚基之间的连接蛋白。然而,尚未鉴定出其他连接蛋白介导微管与GABA(A)受体其余亚基的连接。在本研究中,我们鉴定出了人GABARAP的三个旁系同源物(GABARAPL1、GABARAPL2和GABARAPL3)以及两个小鼠直系同源物(Gabarapl1和Gabarapl2),它们都编码117个氨基酸,与Gabarapl相同。GABARAPL1、GABARAPL2和GABARAP在16种成人组织中的表达模式表明它们在全身广泛表达。作为一种2.3 kb转录本的GABARAPL1在脑、心脏、外周血白细胞、肝脏、肾脏、胎盘和骨骼肌中的表达水平非常高,在胸腺和小肠中非常低,在其他测试组织中为中等水平。GABARAPL2独特的1.35 kb转录本在心脏、脑、睾丸、前列腺、卵巢、脾脏和骨骼肌中高水平表达,在肺、胸腺和小肠中非常低水平表达,在其他测试组织中为中等水平。对于GABARAP,一个1.3 kb的转录本在所有测试组织中均大量表达,差异较小。Gabarapl1和Gabarapl2的表达模式与其在人类中的对应物相似。此外,通过RH定位,GABARAPL1定位于人染色体12p12.3,GABARAPL2定位于16q22.3 - q24.1,而通过搜索相关数据库发现GABARAP和GABARAPL3分别定位于染色体17p13.2和15q25.1。cDNA及其相应基因组序列的序列比较表明,GABARAP、GABARAPL1和GABARAPL2各由四个外显子组成,而GABARAPL3仅分布在一个外显子中。

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