title: FGT-1 is a mammalian GLUT2-like facilitative glucose transporter in Caenorhabditis elegans whose malfunction induces fat accumulation in intestinal cells.
abstract: Caenorhabditis elegans (C. elegans) is an attractive animal model for biological and biomedical research because it permits relatively easy genetic dissection of cellular pathways, including insulin/IGF-like signaling (IIS), that are conserved in mammalian cells. To explore C. elegans as a model system to study the regulation of the facilitative glucose transporter (GLUT), we have characterized the GLUT gene homologues in C. elegans: fgt-1, R09B5.11, C35A11.4, F53H8.3, F48E3.2, F13B12.2, Y61A9LA.1, K08F9.1 and Y37A1A.3. The exogenous expression of these gene products in Xenopus oocytes showed transport activity to unmetabolized glucose analogue 2-deoxy-D-glucose only in FGT-1. The FGT-1-mediated transport activity was inhibited by the specific GLUT inhibitor phloretin and exhibited a Michaelis constant (Km) of 2.8 mM. Mannose, galactose, and fructose were able to inhibit FGT-1-mediated 2-deoxy-D-glucose uptake (P < 0.01), indicating that FGT-1 is also able to transport these hexose sugars. A GFP fusion protein of FGT-1 was observed only on the basolateral membrane of digestive tract epithelia in C. elegans, but not in other tissues. FGT-1::eGFP expression was observed from early embryonic stages. The knockdown or mutation of fgt-1 resulted in increased fat staining in both wild-type and daf-2 (mammalian insulin receptor homologue) mutant animals. Other common phenotypes of IIS mutant animals, including dauer formation and brood size reduction, were not affected by fgt-1 knockdown in wild-type or daf-2 mutants. Our results indicated that in C. elegans, FGT-1 is mainly a mammalian GLUT2-like intestinal glucose transporter and is involved in lipid metabolism.
authors.affiliation: Laboratory of Lactation and Metabolic Physiology, Department of Animal Science, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Shun
authors.initials: S
authors.lastname: Kitaoka
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Morielli
authors.forename: Feng-Qi
authors.initials: FQ
authors.lastname: Zhao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology; D049751:Genome, Helminth / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000737:chemistry; D006801:Humans; D007422:Intestines / Q000166:cytology*; D007700:Kinetics; D050356:Lipid Metabolism; D008322:Mammals / Q000378:metabolism*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity; D014981:Xenopus
chemical_list: D029742:Caenorhabditis elegans Proteins; C585488:FGT-1 protein, C elegans; D051246:Glucose Transport Proteins, Facilitative; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; C495692:SLC2A4 protein, human; D005947:Glucose