Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle

Research output: Contribution to journalArticlepeer-review

Authors

  • Yang Liu
  • Elaine V. Hill
  • Donatienne Tyteca
  • Sarah Carpentier
  • Ada Ingvaldsen
  • Didier Vertommen
  • Louise Lantier
  • Marc Foretz
  • Franck Dequiedt
  • Pierre J. Courtoy
  • Christophe Erneux
  • Benoit Viollet
  • Peter R. Shepherd
  • Jeremy M. Tavare
  • Jørgen Jensen
  • Mark H. Rider

Colleges, School and Institutes

External organisations

  • Université Catholique de Louvain
  • University of Bristol
  • Natl. Inst. of Occupational Health
  • Institut Cochin
  • Paris Descartes University
  • Université de Liég
  • Université Libre de Bruxelles
  • University of Auckland

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 insulinstimulated 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 intracellularmembrane 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.

Details

Original languageEnglish
Pages (from-to)195-206
Number of pages12
JournalBiochemical Journal
Volume455
Issue number2
Early online date27 Sep 2013
Publication statusPublished - 15 Oct 2013

Keywords

  • AMP-activated protein kinase (AMPK), Contraction, Glucose uptake, Insulin, Protein kinase B (PKB), PtdIns(3,5)P2