title: FGT-1 is the major glucose transporter in C. elegans and is central to aging pathways.
abstract: Caenorhabditis elegans is widely used as a model for investigation of the relationships between aging, nutrient restriction and signalling via the DAF-2 (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity of the glucose transporters that may link these processes is unknown. We unexpectedly find that of the eight putative GLUT (glucose transporter)-like genes only the two splice variants of one gene have a glucose transport function in an oocyte expression system. We have named this gene fgt-1 (facilitated glucose transporter, isoform 1). We show that knockdown of fgt-1 RNA leads to loss of glucose transport and reduced glucose metabolism in wild-type worms. The FGT-1 glucose transporters of C. elegans thus play a key role in glucose energy supply to C. elegans. Importantly, knockdown of fgt-1 leads to an extension of lifespan equivalent, but not additive, to that observed in daf-2 and age-1 mutant worms. The results of the present study are consistent with DAF-2 and AGE-1 signalling stimulating glucose transport in C. elegans and this process being associated with the longevity phenotype in daf-2 and age-1 mutant worms. We propose that fgt-1 constitutes a common axis for the lifespan extending effects of nutrient restriction and reduced insulin-like peptide signalling.
authors.affiliation: *Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.forename: Barnabas G
authors.initials: BG
authors.lastname: Williams
authors.forename: Françoise
authors.initials: F
authors.lastname: Koumanov
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Wolstenholme
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Holman
mesh_terms: D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D029742:Caenorhabditis elegans Proteins; C585488:FGT-1 protein, C elegans; D051246:Glucose Transport Proteins, Facilitative; D005947:Glucose
references.citation: Aging Cell. 2008 Mar;7(2):199-206
references.pmid: 18221413
references.citation: EMBO J. 2001 Aug 15;20(16):4467-77
references.pmid: 11500374
references.citation: Cell Metab. 2012 Apr 4;15(4):451-65
references.pmid: 22482728
references.citation: Cell Metab. 2008 Aug;8(2):99-104
references.pmid: 18680711
references.citation: J Cell Sci. 2011 Dec 15;124(Pt 24):4147-59
references.pmid: 22247191
references.citation: Biochem J. 2007 Apr 15;403(2):e9-11
references.pmid: 17376030
references.citation: Annu Rev Med. 2001;52:239-57
references.pmid: 11160777
references.citation: J Nat Prod. 2011 Aug 26;74(8):1713-20
references.pmid: 21805983
references.citation: Nature. 1996 Aug 8;382(6591):536-9
references.pmid: 8700226
references.citation: Curr Biol. 2009 Aug 11;19(15):R657-66
references.pmid: 19674551
references.citation: Annu Rev Med. 2003;54:131-52
references.pmid: 12525670
references.citation: J Mol Biol. 2000 Sep 8;302(1):205-17
references.pmid: 10964570
references.citation: PLoS One. 2013 Jun 24;8(6):e68475
references.pmid: 23826391
references.citation: Cell Metab. 2009 Nov;10(5):379-91
references.pmid: 19883616
references.citation: Science. 2007 Jul 20;317(5836):369-72
references.pmid: 17641201
references.citation: Am J Physiol. 1999 Apr;276(4):E728-38
references.pmid: 10198310
references.citation: Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70
references.pmid: 19433800
references.citation: Cell. 2005 Feb 25;120(4):449-60
references.pmid: 15734678
references.citation: J Clin Invest. 2010 Jun;120(6):1791-9
references.pmid: 20516647
references.citation: Biochemistry. 2011 Apr 19;50(15):3048-61
references.pmid: 21405107
references.citation: J Biol Chem. 1994 Apr 15;269(15):11578-83
references.pmid: 8157690
references.citation: Traffic. 2011 Jun;12(6):672-81
references.pmid: 21401839
references.citation: Annu Rev Physiol. 2006;68:123-58
references.pmid: 16460269
references.citation: Biochem J. 1993 Oct 15;295 ( Pt 2):329-41
references.pmid: 8240230
references.citation: Nature. 1993 Dec 2;366(6454):461-4
references.pmid: 8247153
references.citation: Biochim Biophys Acta. 1993 Jun 8;1154(1):17-49
references.pmid: 8507645
references.citation: J Biol Chem. 1992 Sep 5;267(25):17502-7
references.pmid: 1517202
references.citation: PLoS One. 2013 Jun 03;8(6):e65118
references.pmid: 23755179
references.citation: WormBook. 2006 Feb 11;:1-11
references.pmid: 18050451
references.citation: Cell Metab. 2007 Oct;6(4):280-93
references.pmid: 17908557
references.citation: Nature. 2012 Oct 18;490(7420):361-6
references.pmid: 23075985
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):85-96
references.pmid: 16493415
references.citation: J Nutr Biochem. 2005 Mar;16(3):129-37
references.pmid: 15741046
references.citation: Aging Cell. 2007 Dec;6(6):827-39
references.pmid: 18001293
references.citation: Nature. 2011 Sep 21;477(7365):482-5
references.pmid: 21938067
references.citation: Aging Cell. 2006 Dec;5(6):487-94
references.pmid: 17081160
references.citation: Nature. 2004 Aug 5;430(7000):686-9
references.pmid: 15254550
references.citation: Science. 2009 Oct 2;326(5949):140-4
references.pmid: 19797661
references.citation: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5587-91
references.pmid: 8202531
references.citation: Biochem J. 1994 Jun 1;300 ( Pt 2):291-4
references.pmid: 8002929
references.citation: JAMA. 2006 Apr 5;295(13):1539-48
references.pmid: 16595757
references.citation: Bioinformatics. 1998;14(4):378-9
references.pmid: 9632836
references.citation: Biochem J. 1998 Jan 15;329 ( Pt 2):289-93
references.pmid: 9425111
references.citation: Nat Rev Mol Cell Biol. 2007 Sep;8(9):681-91
references.pmid: 17684529
references.citation: Science. 1997 Aug 15;277(5328):942-6
references.pmid: 9252323
references.citation: J Cell Sci. 2002 Jan 1;115(Pt 1):131-40
references.pmid: 11801731
references.citation: Annu Rev Biochem. 2012;81:507-32
references.pmid: 22482906
references.citation: JAMA. 2002 Jan 16;287(3):360-72
references.pmid: 11790216
references.citation: Mech Ageing Dev. 2005 Sep;126(9):913-22
references.pmid: 15885745
references.citation: Br J Pharmacol. 2003 Oct;140(3):487-99
references.pmid: 12970085
references.citation: Genetics. 1988 Jan;118(1):75-86
references.pmid: 8608934