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.
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Research Article|
September 27 2013
Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle
Yang Liu;
Yang Liu
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Yu-Chiang Lai;
Yu-Chiang Lai
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Elaine V. Hill;
Elaine V. Hill
†Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K
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Donatienne Tyteca;
Donatienne Tyteca
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Sarah Carpentier;
Sarah Carpentier
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Ada Ingvaldsen;
Ada Ingvaldsen
‡National Institute of Occupational Health, Pb 8149 Dep, Oslo, Norway
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Didier Vertommen;
Didier Vertommen
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Louise Lantier;
Louise Lantier
§INSERM, U1016, Institut Cochin, 22 rue Méchain, 75014 Paris, France
∥CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
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Marc Foretz;
Marc Foretz
§INSERM, U1016, Institut Cochin, 22 rue Méchain, 75014 Paris, France
∥CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
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Franck Dequiedt;
Franck Dequiedt
¶Laboratory of Protein Signaling and Interactions, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), University of Liège, Start-Tilman, B-4000 Liège, Belgium
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Pierre J. Courtoy;
Pierre J. Courtoy
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
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Christophe Erneux;
Christophe Erneux
**IRIBHM, Campus Erasme, ULB Bâtiment C, 808 route de Lennik, B-1070 Brussels, Belgium
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Benoît Viollet;
Benoît Viollet
§INSERM, U1016, Institut Cochin, 22 rue Méchain, 75014 Paris, France
∥CNRS, UMR8104, Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France
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Peter R. Shepherd;
Peter R. Shepherd
††Maurice Wilkins Centre for Molecular Biodiscovery and Department of Molecular Medicine and Pathology, University of Auckland, Auckland 1042, New Zealand
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Jeremy M. Tavaré;
Jeremy M. Tavaré
†Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K
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Jørgen Jensen;
Jørgen Jensen
‡National Institute of Occupational Health, Pb 8149 Dep, Oslo, Norway
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Mark H. Rider
Mark H. Rider
1
*Université catholique de Louvain, de Duve Institute, Avenue Hippocrate, 75, B-1200 Brussels, Belgium
1To whom correspondence should be addressed (email mark.rider@uclouvain.be).
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Publisher: Portland Press Ltd
Received:
May 09 2013
Revision Received:
July 31 2013
Accepted:
August 01 2013
Accepted Manuscript online:
August 01 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 455 (2): 195–206.
Article history
Received:
May 09 2013
Revision Received:
July 31 2013
Accepted:
August 01 2013
Accepted Manuscript online:
August 01 2013
Connected Content
A commentary has been published:
PIKfyve: a new fish in the growing pool of AMPK substrates
Citation
Yang Liu, Yu-Chiang Lai, Elaine V. Hill, Donatienne Tyteca, Sarah Carpentier, Ada Ingvaldsen, Didier Vertommen, Louise Lantier, Marc Foretz, Franck Dequiedt, Pierre J. Courtoy, Christophe Erneux, Benoît Viollet, Peter R. Shepherd, Jeremy M. Tavaré, Jørgen Jensen, Mark H. Rider; Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle. Biochem J 15 October 2013; 455 (2): 195–206. doi: https://doi.org/10.1042/BJ20130644
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