title: Functional consequences of an in vivo mutation in exon 10 of the human GLUT1 gene.
abstract: 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.
authors.affiliation: Institute of Pharmacology, Freie Universität Berlin, Thielallee 67-73, D-14195 Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.forename: Elena
authors.initials: E
authors.lastname: Gertsen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Monden
authors.forename: Jörg
authors.initials: J
authors.lastname: Klepper
authors.forename: Konrad
authors.initials: K
authors.lastname: Keller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western / Q000379:methods; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons / Q000235:genetics*; D016368:Frameshift Mutation / Q000235:genetics*; D051272:Glucose Transporter Type 1; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D014316:Tritium; D014982:Xenopus laevis
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D014316:Tritium; C037626:3'-O-methylguanosine; D006151:Guanosine; D003571:Cytochalasin B; D003847:Deoxyglucose