Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene
Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene
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DOI：
10.1016/s0014-5793(03)01247-x
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发表时间：
2003-12-04
期刊：
影响因子：
3.5
通讯作者：
Keller, K
中科院分区：
文献类型：
--
作者：
Lange, P;Gertsen, E;Keller, K
研究了人易化葡萄糖转运蛋白亚型1（GLUT 1）基因体内杂合插入突变的功能后果。由此产生的移码在外显子10中改变了C-末端的一级结构，从天然GLUT 1中的42个氨基酸残基到突变体中的61个氨基酸残基。通过在非洲爪蟾卵母细胞中表达突变体cDNA证实了对患者红细胞的动力学研究。Km和Vmax值明显降低，说明致病性。突变体和野生型GLUT 1对质膜的靶向相当。细胞松弛素B的转运抑制作用在突变体中比在野生型转运体中更有效。GLUT 1的底物特异性保持不变。(C)2003年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
The functional consequences of an in vivo heterozygous insertion mutation in the human facilitated glucose transporter isoform 1 (GLUT1) gene were investigated. The resulting frameshift in exon 10 changed the primary structure of the C-terminus from 42 in native GLUT1 to 61 amino acid residues in the mutant. Kinetic studies on a patient's erythrocytes were substantiated by expressing the mutant cDNA in Xenopus laevis oocytes. K-m and V-max values were clearly decreased explaining pathogenicity. Targeting to the plasma membrane was comparable between mutant and wild-type GLUT1. Transport inhiblition by cytochalasin B was more effective in the mutant than in the wild-type transporter. The substrate specificity of GLUT1 remained unchanged. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.