title: Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle.
abstract: PIKfyve (FYVE domain-containing phosphatidylinositol 3-phosphate 5-kinase), the lipid kinase that phosphorylates PtdIns3P to PtdIns(3,5)P2, has been implicated in insulin-stimulated glucose uptake. We investigated whether PIKfyve could also be involved in contraction/AMPK (AMP-activated protein kinase)-stimulated glucose uptake in skeletal muscle. Incubation of rat epitrochlearis muscles with YM201636, a selective PIKfyve inhibitor, reduced contraction- and AICAriboside (5-amino-4-imidazolecarboxamide riboside)-stimulated glucose uptake. Consistently, PIKfyve knockdown in C2C12 myotubes reduced AICAriboside-stimulated glucose transport. Furthermore, muscle contraction increased PtdIns(3,5)P2 levels and PIKfyve phosphorylation. AMPK phosphorylated PIKfyve at Ser307 both in vitro and in intact cells. Following subcellular fractionation, PIKfyve recovery in a crude intracellular membrane fraction was increased in contracting versus resting muscles. Also in opossum kidney cells, wild-type, but not S307A mutant, PIKfyve was recruited to endosomal vesicles in response to AMPK activation. We propose that PIKfyve activity is required for the stimulation of skeletal muscle glucose uptake by contraction/AMPK activation. PIKfyve is a new AMPK substrate whose phosphorylation at Ser307 could promote PIKfyve translocation to endosomes for PtdIns(3,5)P2 synthesis to facilitate GLUT4 (glucose transporter 4) translocation.
authors.affiliation: *Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu-Chiang
authors.initials: YC
authors.lastname: Lai
authors.forename: Elaine V
authors.initials: EV
authors.lastname: Hill
authors.forename: Donatienne
authors.initials: D
authors.lastname: Tyteca
authors.forename: Sarah
authors.initials: S
authors.lastname: Carpentier
authors.forename: Ada
authors.initials: A
authors.lastname: Ingvaldsen
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.forename: Louise
authors.initials: L
authors.lastname: Lantier
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Franck
authors.initials: F
authors.lastname: Dequiedt
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Christophe
authors.initials: C
authors.lastname: Erneux
authors.forename: Benoît
authors.initials: B
authors.lastname: Viollet
authors.forename: Peter R
authors.initials: PR
authors.lastname: Shepherd
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Tavaré
authors.forename: Jørgen
authors.initials: J
authors.lastname: Jensen
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rider
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism*; D009893:Opossums; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; C106336:phosphatidylinositol 3,5-diphosphate; D000620:Aminoimidazole Carboxamide; C031340:imidazolecarboxamide; D058539:Phosphatidylinositol 3-Kinase; D055372:AMP-Activated Protein Kinases; D005947:Glucose