LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine
LAT2, a new basolateral 4F2hc/CD98-associated amino acid transporter of kidney and intestine
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DOI：
10.1074/jbc.274.49.34948
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发表时间：
1999-12-03
影响因子：
4.8
通讯作者：
Kühn, LC
中科院分区：
文献类型：
--
作者：
Rossier, G;Meier, C;Kühn, LC
糖蛋白相关氨基酸转运体(GpaAT)是与通透酶相关的蛋白质，需要异源二聚体才能表达其功能。到目前为止，已有4个脊椎动物gpaAT与4F2hc/CD98功能表达相关，而1个gpaAT与rBAT特异性相关。在这项研究中，我们鉴定了一种新的gpaAT，LAT2，它通过表达序列标签数据库搜索来识别小鼠和人的cDNA。编码的同源蛋白全长531个，氨基酸长度为92%。它们与gpaATs LAT1和y(+)LAT1分别有52%和48%的残基。当小鼠LAT2和人4F2hc CRNAs共同注射到非洲爪哇卵母细胞中时，形成了二硫键连接的杂二聚体，并诱导了L式的氨基酸摄取，这与LAT1-4F2hc产生的氨基酸摄取略有不同：对L-苯丙氨酸的表观亲和力更高，L-丙氨酸在生理浓度下被转运。在外源氨基酸底物存在的情况下，LAT2-4F2hc也介导了氨基酸外流。LAT2基因主要在肾脏和肠道表达，而LAT1基因广泛表达。免疫荧光实验显示，4F2hc和LAT2共定位于肾近端小管和小肠上皮细胞的基底外侧膜。综上所述，LAT2与LAT1形成了L型gpaATs的一个亚家族，我们认为LAT1参与了细胞内氨基酸的摄取，而LAT2则参与了上皮氨基酸的吸收。
Glycoprotein-associated amino acid transporters (gpaAT) are permease-related proteins that require heterodimerization to express their function. So far, four vertebrate gpaATs have been shown to associate with 4F2hc/CD98 for functional expression, whereas one gpaAT specifically associates with rBAT. In this study, we characterized a novel gpaAT, LAT2, for which mouse and human cDNAs were identified by expressed sequence tag data base searches. The encoded ortholog proteins are 531 and 535 amino acids long and 92% identical. They share 52 and 48% residues with the gpaATs LAT1 and y(+)LAT1, respectively. When mouse LAT2 and human 4F2hc cRNAs were co-injected into Xenopus oocytes, disulfide-linked heterodimers were formed, and an L-type amino acid uptake was induced, which differed slightly from that produced by LAT1-4F2hc: the apparent affinity for L-phenylalanine was higher, and L-alanine was transported at physiological concentrations. In the presence of an external amino acid substrate, LAT2-4F2hc also mediated amino acid efflux. LAT2 mRNA is expressed mainly in kidney and intestine, whereas LAT1 mRNA is expressed widely. Immunofluorescence experiments showed colocalization of 4F2hc and LAT2 at the basolateral membrane of kidney proximal tubules and small intestine epithelia. In conclusion, LAT2 forms with LAT1 a subfamily of L-type gpaATs, We propose that LAT1 is involved in cellular amino acid uptake, whereas LAT2 plays a role in epithelial amino acid (re)absorption.