title: ATM and GLUT1-S490 phosphorylation regulate GLUT1 mediated transport in skeletal muscle.
abstract: OBJECTIVE
  The glucose and dehydroascorbic acid (DHA) transporter GLUT1 contains a phosphorylation site, S490, for ataxia telangiectasia mutated (ATM). The objective of this study was to determine whether ATM and GLUT1-S490 regulate GLUT1.
  
  
  METHODS
  L6 myoblasts and mouse skeletal muscles were used to study the effects of ATM inhibition, ATM activation, and S490 mutation on GLUT1 localization, trafficking, and transport activity.
  
  
  RESULTS
  In myoblasts, inhibition of ATM significantly diminished cell surface GLUT1, glucose and DHA transport, GLUT1 externalization, and association of GLUT1 with Gα-interacting protein-interacting protein, C-terminus (GIPC1), which has been implicated in recycling of endosomal proteins. In contrast, ATM activation by doxorubicin (DXR) increased DHA transport, cell surface GLUT1, and the GLUT1/GIPC1 association. S490A mutation decreased glucose and DHA transport, cell surface GLUT1, and interaction of GLUT1 with GIPC1, while S490D mutation increased transport, cell surface GLUT1, and the GLUT1/GIPC1 interaction. ATM dysfunction or ATM inhibition reduced DHA transport in extensor digitorum longus (EDL) muscles and decreased glucose transport in EDL and soleus. In contrast, DXR increased DHA transport in EDL.
  
  
  CONCLUSIONS
  These results provide evidence that ATM and GLUT1-S490 promote cell surface GLUT1 and GLUT1-mediated transport in skeletal muscle associated with upregulation of the GLUT1/GIPC1 interaction.
authors.affiliation: Department of Biology, Saint Louis University, St. Louis, Missouri, United States of America.
authors.forename: Stanley
authors.initials: S
authors.lastname: Andrisse
authors.forename: Gaytri D
authors.initials: GD
authors.lastname: Patel
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Chen
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Webber
authors.forename: Larry D
authors.initials: LD
authors.lastname: Spears
authors.forename: Rikki M
authors.initials: RM
authors.lastname: Koehler
authors.forename: Rona M
authors.initials: RM
authors.lastname: Robinson-Hill
authors.forename: James K
authors.initials: JK
authors.lastname: Ching
authors.forename: Imju
authors.initials: I
authors.lastname: Jeong
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Fisher
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics / Q000502:physiology; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051272:Glucose Transporter Type 1; D064007:Ataxia Telangiectasia Mutated Proteins