title: Mechanisms of expression and translocation of major fission yeast glucose transporters regulated by CaMKK/phosphatases, nuclear shuttling, and TOR.
abstract: Hexose transporters are required for cellular glucose uptake; thus they play a pivotal role in glucose homeostasis in multicellular organisms. Using fission yeast, we explored hexose transporter regulation in response to extracellular glucose concentrations. The high-affinity transporter Ght5 is regulated with regard to transcription and localization, much like the human GLUT transporters, which are implicated in diabetes. When restricted to a glucose concentration equivalent to that of human blood, the fission yeast transcriptional regulator Scr1, which represses Ght5 transcription in the presence of high glucose, is displaced from the nucleus. Its displacement is dependent on Ca(2+)/calmodulin-dependent kinase kinase, Ssp1, and Sds23 inhibition of PP2A/PP6-like protein phosphatases. Newly synthesized Ght5 locates preferentially at the cell tips with the aid of the target of rapamycin (TOR) complex 2 signaling. These results clarify the evolutionarily conserved molecular mechanisms underlying glucose homeostasis, which are essential for preventing hyperglycemia in humans.
authors.affiliation: Institute of Life Science, Kurume University, Hyakunen-Kohen 1-1, Kurume, Fukuoka 839-0864, Japan saitou_shigeaki@kurume-u.ac.jp myanagid@gmail.com.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Okinawa Institute Science and Technology Graduate University, Tancha 1919-1, Onna, Okinawa 904-0495, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Mori
authors.affiliation: Okinawa Institute Science and Technology Graduate University, Tancha 1919-1, Onna, Okinawa 904-0495, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Uehara
authors.affiliation: Institute of Life Science, Kurume University, Hyakunen-Kohen 1-1, Kurume, Fukuoka 839-0864, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Masuda
authors.affiliation: Institute of Life Science, Kurume University, Hyakunen-Kohen 1-1, Kurume, Fukuoka 839-0864, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Soejima
authors.affiliation: Okinawa Institute Science and Technology Graduate University, Tancha 1919-1, Onna, Okinawa 904-0495, Japan saitou_shigeaki@kurume-u.ac.jp myanagid@gmail.com.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D000076225:Mechanistic Target of Rapamycin Complex 2; D008856:Microscopy, Fluorescence; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D018797:Cell Cycle Proteins; C000601636:Ght5 protein, S pombe; D051246:Glucose Transport Proteins, Facilitative; D018840:HSP70 Heat-Shock Proteins; D009004:Monosaccharide Transport Proteins; D046912:Multiprotein Complexes; C111935:PSS1 protein, S pombe; D020033:Protein Isoforms; D029702:Schizosaccharomyces pombe Proteins; C103137:Sds23 protein, S pombe; D049452:Green Fluorescent Proteins; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D010749:Phosphoprotein Phosphatases; D005947:Glucose