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来自大鼠空肠上皮的一个编码具有y+L系统氨基酸转运活性的蛋白质(4F2hc)的cDNA的克隆及功能表达。

Cloning and functional expression of a cDNA from rat jejunal epithelium encoding a protein (4F2hc) with system y+L amino acid transport activity.

作者信息

Yao S Y, Muzyka W R, Elliott J F, Cheeseman C I, Young J D

机构信息

Membrane Transport Research Group, Department of Physiology, Medical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.

出版信息

Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):745-52. doi: 10.1042/bj3300745.

DOI:10.1042/bj3300745
PMID:9480885
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1219200/
Abstract

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.

摘要

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。

相似文献

1
Cloning and functional expression of a cDNA from rat jejunal epithelium encoding a protein (4F2hc) with system y+L amino acid transport activity.来自大鼠空肠上皮的一个编码具有y+L系统氨基酸转运活性的蛋白质(4F2hc)的cDNA的克隆及功能表达。
Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):745-52. doi: 10.1042/bj3300745.
2
Stimulation of system y(+)-like amino acid transport by the heavy chain of human 4F2 surface antigen in Xenopus laevis oocytes.非洲爪蟾卵母细胞中人类4F2表面抗原重链对系统y(+)-样氨基酸转运的刺激作用。
Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5606-10. doi: 10.1073/pnas.89.12.5606.
3
Evidence that the transport-related proteins BAT and 4F2hc are not specific for amino acids: induction of Na+-dependent uridine and pyruvate transport activity by recombinant BAT and 4F2hc expressed in Xenopus oocytes.与转运相关的蛋白BAT和4F2hc并非氨基酸特异性蛋白的证据:非洲爪蟾卵母细胞中表达的重组BAT和4F2hc对Na⁺依赖性尿苷和丙酮酸转运活性的诱导作用。
Biochem Cell Biol. 1998;76(5):859-65. doi: 10.1139/bcb-76-5-859.
4
The 4F2hc surface antigen is necessary for expression of system L-like neutral amino acid-transport activity in C6-BU-1 rat glioma cells: evidence from expression studies in Xenopus laevis oocytes.4F2hc表面抗原对于C6-BU-1大鼠胶质瘤细胞中L-型中性氨基酸转运活性的表达是必需的:来自非洲爪蟾卵母细胞表达研究的证据。
Biochem J. 1995 Dec 15;312 ( Pt 3)(Pt 3):863-70. doi: 10.1042/bj3120863.
5
Poly(A)+ RNA from the mucosa of rat jejunum induces novel Na(+)-dependent and Na(+)-independent leucine transport activities in in oocytes of Xenopus laevis.来自大鼠空肠黏膜的多聚腺苷酸(Poly(A))+ RNA 在非洲爪蟾卵母细胞中诱导出新型的依赖钠(Na(+))和不依赖钠(Na(+))的亮氨酸转运活性。
Mol Membr Biol. 1994 Apr-Jun;11(2):109-18. doi: 10.3109/09687689409162228.
6
Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.鉴定出一种膜蛋白LAT-2,它与4F2重链共表达,具有对两性离子型小氨基酸和大氨基酸具有广泛特异性的L型氨基酸转运活性。
J Biol Chem. 1999 Jul 9;274(28):19738-44. doi: 10.1074/jbc.274.28.19738.
7
Cloning and expression of a b(0,+)-like amino acid transporter functioning as a heterodimer with 4F2hc instead of rBAT. A new candidate gene for cystinuria.一种与4F2hc而非rBAT形成异源二聚体发挥作用的b(0, +)样氨基酸转运体的克隆与表达。胱氨酸尿症的一个新候选基因。
J Biol Chem. 1999 Oct 8;274(41):29005-10. doi: 10.1074/jbc.274.41.29005.
8
Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance.一种与4F2hc相关联以编码氨基酸转运活性y + L的膜蛋白(y + L氨基酸转运体-1)的鉴定与表征。赖氨酸尿性蛋白不耐受的一个候选基因。
J Biol Chem. 1998 Dec 4;273(49):32437-45. doi: 10.1074/jbc.273.49.32437.
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A new family of proteins (rBAT and 4F2hc) involved in cationic and zwitterionic amino acid transport: a tale of two proteins in search of a transport function.参与阳离子和两性离子氨基酸转运的新蛋白质家族(rBAT和4F2hc):两种寻找转运功能的蛋白质的故事
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Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.一种具有广泛底物选择性的非Na⁺依赖性中性氨基酸转运体的鉴定及功能表征。
J Biol Chem. 1999 Jul 9;274(28):19745-51. doi: 10.1074/jbc.274.28.19745.

引用本文的文献

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2
Small bowel review: normal physiology part 1.小肠综述:正常生理学 第1部分
Dig Dis Sci. 2001 Dec;46(12):2567-87. doi: 10.1023/a:1012794505897.
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Adaptive regulation of intestinal lysine metabolism.肠道赖氨酸代谢的适应性调节。
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11620-5. doi: 10.1073/pnas.200371497.

本文引用的文献

1
A SURVEY OF THE EFFECT OF OTHER AMINO-ACIDS ON THE ABSORPTION OF L-ARGININE AND L-LYSINE BY THE RAT INTESTINE.其他氨基酸对大鼠肠道吸收L-精氨酸和L-赖氨酸影响的研究
Gastroenterologia. 1964;101:330-8. doi: 10.1159/000202330.
2
Demonstration of system y+L activity on the basal plasma membrane surface of rat placenta and developmentally regulated expression of 4F2HC mRNA.大鼠胎盘基底质膜表面系统y+L活性的证实及4F2HC mRNA的发育调控表达。
Placenta. 1997 Nov;18(8):643-8. doi: 10.1016/s0143-4004(97)90005-9.
3
Electrogenic L-histidine transport in neutral and basic amino acid transporter (NBAT)-expressing Xenopus laevis oocytes. Evidence for two functionally distinct transport mechanisms induced by NBAT expression.在表达中性和碱性氨基酸转运体(NBAT)的非洲爪蟾卵母细胞中的电生性L-组氨酸转运。NBAT表达诱导两种功能不同的转运机制的证据。
J Biol Chem. 1997 Jan 3;272(1):125-30.
4
Genomic structure and organization of the human rBAT gene (SLC3A1).人类rBAT基因(SLC3A1)的基因组结构与组织
Genomics. 1996 Oct 15;37(2):249-52. doi: 10.1006/geno.1996.0552.
5
Multiple components of arginine and phenylalanine transport induced in neutral and basic amino acid transporter-cRNA-injected Xenopus oocytes.在注射了中性和碱性氨基酸转运体-cRNA的非洲爪蟾卵母细胞中诱导产生的精氨酸和苯丙氨酸转运的多种成分。
Biochem J. 1996 Sep 15;318 ( Pt 3)(Pt 3):915-22. doi: 10.1042/bj3180915.
6
Phenotype characterization and prevalence of rBAT M467T mutation in Italian cystinuric patients.意大利胱氨酸尿症患者中rBAT M467T突变的表型特征及患病率
J Inherit Metab Dis. 1996;19(2):243-5. doi: 10.1007/BF01799440.
7
The binding specificity of amino acid transport system y+L in human erythrocytes is altered by monovalent cations.人红细胞中氨基酸转运系统y+L的结合特异性会因单价阳离子而改变。
J Membr Biol. 1996 Sep;153(1):37-44. doi: 10.1007/s002329900107.
8
L-lysine transport in chicken jejunal brush border membrane vesicles.鸡空肠刷状缘膜囊泡中的L-赖氨酸转运
J Membr Biol. 1996 Aug;152(3):183-93. doi: 10.1007/s002329900096.
9
Obligatory amino acid exchange via systems bo,+-like and y+L-like. A tertiary active transport mechanism for renal reabsorption of cystine and dibasic amino acids.通过类bo,+-和类y+L系统进行必需氨基酸交换。一种用于肾脏重吸收胱氨酸和二碱基氨基酸的三级主动转运机制。
J Biol Chem. 1996 Jul 26;271(30):17761-70. doi: 10.1074/jbc.271.30.17761.
10
The rBAT gene is responsible for L-cystine uptake via the b0,(+)-like amino acid transport system in a "renal proximal tubular" cell line (OK cells).rBAT基因通过b0,(+)-样氨基酸转运系统负责在“肾近端小管”细胞系(OK细胞)中摄取L-胱氨酸。
J Biol Chem. 1996 May 3;271(18):10569-76. doi: 10.1074/jbc.271.18.10569.