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Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene
Author(s) -
Lange Peter,
Gertsen Elena,
Monden Ingrid,
Klepper Jörg,
Keller Konrad
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01247-x
Subject(s) - frameshift mutation , mutant , glut1 , xenopus , exon , microbiology and biotechnology , mutation , biology , gene isoform , glucose transporter type 1 , glucose transporter , in vivo , gene , biochemistry , chemistry , genetics , endocrinology , insulin
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 inhibition by cytochalasin B was more effective in the mutant than in the wild‐type transporter. The substrate specificity of GLUT1 remained unchanged.