Characterization of the human SLC2A11 (GLUT11) gene: alternative promoter usage, function, expression, and subcellular distribution of three isoforms, and lack of mouse orthologue.
GLUT11 (SLC2A11) is a class II sugar transport facilitator which exhibits highest similarity with the fructose transporter GLUT5 (about 42%). Here we demonstrate that separate exons 1 (exon 1A, exon 1B, and exon 1C) of the SLC2A11 gene generate mRNAs of three GLUT11 variants (GLUT11-A, GLUT11-B, and GLUT11-C) that differ in the amino acid sequence of their N-termini. All three 5'-flanking regions of exon 1A, exon 1B and exon 1C exhibited promoter activity when expressed as luciferase fusion constructs in COS-7 cells. 5'-RACE-PCR, quantitative real-time PCR, and Northern blot analysis performed with specific probes for exon 1A, 1B and 1C demonstrated that GLUT11-A is expressed in heart, skeletal muscle, and kidney, GLUT11-B in kidney, adipose tissue, and placenta, and GLUT11-C in adipose tissue, heart, skeletal muscle, and pancreas. Surprisingly, mice and rats lack the SLC2A11 gene. When expressed in Xenopus oocytes, all three GLUT11 isoforms transport glucose and fructose but not galactose. There was no apparent difference in the subcellular distribution of the three isoforms expressed in COS-7 cells. Our data indicate that different promoters and splicing of the human SLC2A11 gene generate three GLUT11 isoforms which are expressed in a tissue specific manner but do not appear to differ in their functional characteristics.
Scheepers
Andrea
A
Department of Pharmacology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.
Schmidt
Stefan
S
Manolescu
Andrei
A
Cheeseman
Chris I
CI
Bell
Andreas
A
Zahn
Claudia
C
Joost
Hans-Georg
HG
Schürmann
Annette
A
D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity / Q000235:genetics; D014158:Transcription, Genetic; D014982:Xenopus laevis
D051246:Glucose Transport Proteins, Facilitative; D020033:Protein Isoforms; D012333:RNA, Messenger; C439386:SLC2A11 protein, human; D005947:Glucose