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氨基酸转运系统N新亚型的克隆及功能特性分析

Cloning and functional characterization of a new subtype of the amino acid transport system N.

作者信息

Nakanishi T, Kekuda R, Fei Y J, Hatanaka T, Sugawara M, Martindale R G, Leibach F H, Prasad P D, Ganapathy V

机构信息

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912, USA.

出版信息

Am J Physiol Cell Physiol. 2001 Dec;281(6):C1757-68. doi: 10.1152/ajpcell.2001.281.6.C1757.

DOI:10.1152/ajpcell.2001.281.6.C1757
PMID:11698233
Abstract

We have cloned a new subtype of the amino acid transport system N2 (SN2 or second subtype of system N) from rat brain. Rat SN2 consists of 471 amino acids and belongs to the recently identified glutamine transporter gene family that consists of system N and system A. Rat SN2 exhibits 63% identity with rat SN1. It also shows considerable sequence identity (50-56%) with the members of the amino acid transporter A subfamily. In the rat, SN2 mRNA is most abundant in the liver but is detectable in the brain, lung, stomach, kidney, testis, and spleen. When expressed in Xenopus laevis oocytes and in mammalian cells, rat SN2 mediates Na(+)-dependent transport of several neutral amino acids, including glycine, asparagine, alanine, serine, glutamine, and histidine. The transport process is electrogenic, Li(+) tolerant, and pH sensitive. The transport mechanism involves the influx of Na(+) and amino acids coupled to the efflux of H(+), resulting in intracellular alkalization. Proline, alpha-(methylamino)isobutyric acid, and anionic and cationic amino acids are not recognized by rat SN2.

摘要

我们已经从大鼠脑中克隆出氨基酸转运系统N2的一种新亚型(SN2或系统N的第二种亚型)。大鼠SN2由471个氨基酸组成,属于最近鉴定出的谷氨酰胺转运体基因家族,该家族由系统N和系统A组成。大鼠SN2与大鼠SN1的同源性为63%。它与氨基酸转运体A亚家族的成员也具有相当高的序列同源性(50 - 56%)。在大鼠中,SN2 mRNA在肝脏中含量最高,但在脑、肺、胃、肾、睾丸和脾脏中也可检测到。当在非洲爪蟾卵母细胞和哺乳动物细胞中表达时,大鼠SN2介导几种中性氨基酸的Na⁺依赖性转运,包括甘氨酸、天冬酰胺、丙氨酸、丝氨酸、谷氨酰胺和组氨酸。转运过程是生电的,对Li⁺耐受,且对pH敏感。转运机制涉及Na⁺和氨基酸的内流与H⁺的外流偶联,导致细胞内碱化。大鼠SN2不识别脯氨酸、α - (甲基氨基)异丁酸以及阴离子和阳离子氨基酸。

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