Yao S Y, Muzyka W R, Elliott J F, Cheeseman C I, Young J D
Membrane Transport Research Group, Department of Physiology, Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):745-52. doi: 10.1042/bj3300745.
Two different protein families, designated CAT (cationic amino acid transporter) and BAT (broad-specificity amino acid transporter) mediate the plasma membrane transport of cationic amino acids in animal cells. CAT transporters have 12-14 transmembrane domains and are selective for cationic amino acids. BAT proteins, in contrast, have one to four transmembrane domains and induce the transport of both cationic and zwitterionic amino acids when expressed in Xenopus oocytes. Mutations in the human BAT gene cause type I cystinuria, a disease affecting the ability of intestinal and renal brush border membranes to transport cationic amino acids and cystine. We have used functional expression cloning in oocytes to isolate a BAT-related cDNA from rat jejunal epithelium. The cDNA encodes the rat 4F2 heavy chain (4F2hc) cell-surface antigen, a 527-residue (60 kDa) protein that is 26% identical in amino acid sequence with rat renal BAT (also known as NBAT/D2). Expression of rat jejunal 4F2hc in oocytes induced the lysine-inhibitable Na+-dependent influx of leucine and the leucine-inhibitable Na+-independent influx of lysine. Lysine efflux was stimulated by extracellular (Na+ plus leucine). These characteristics identify the expressed amino acid transport activity as system y+L, a transporter that has been implicated in basal membrane transport of cationic amino acids in intestine, kidney and placenta.
有两类不同的蛋白质家族,分别称为阳离子氨基酸转运体(CAT)和广泛特异性氨基酸转运体(BAT),介导动物细胞中阳离子氨基酸的质膜转运。CAT转运体有12 - 14个跨膜结构域,对阳离子氨基酸具有选择性。相比之下,BAT蛋白有1至4个跨膜结构域,当在非洲爪蟾卵母细胞中表达时,可诱导阳离子和两性离子氨基酸的转运。人类BAT基因突变会导致I型胱氨酸尿症,这是一种影响肠道和肾刷状缘膜转运阳离子氨基酸和胱氨酸能力的疾病。我们利用卵母细胞中的功能表达克隆技术,从大鼠空肠上皮中分离出一个与BAT相关的cDNA。该cDNA编码大鼠4F2重链(4F2hc)细胞表面抗原,这是一种由527个氨基酸残基组成(60 kDa)的蛋白质,其氨基酸序列与大鼠肾BAT(也称为NBAT/D2)有26%的同源性。大鼠空肠4F2hc在卵母细胞中的表达诱导了亮氨酸的赖氨酸抑制性Na⁺依赖性内流以及赖氨酸的亮氨酸抑制性非Na⁺依赖性内流。赖氨酸外流受到细胞外(Na⁺加亮氨酸)的刺激。这些特性将所表达的氨基酸转运活性确定为y⁺L系统,该转运体与肠道、肾脏和胎盘基底膜中阳离子氨基酸的转运有关。