1. Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle
- Author
-
Mark H. Rider, Ada Ingvaldsen, Yu-Chiang Lai, Didier Vertommen, Peter R. Shepherd, Louise Lantier, Jeremy M. Tavaré, Christophe Erneux, Jørgen Jensen, Pierre J. Courtoy, Elaine V. Hill, Marc Foretz, Franck Dequiedt, Yang Liu, Sarah Carpentier, Benoit Viollet, and Donatienne Tyteca
- Subjects
Male ,medicine.medical_specialty ,Glucose uptake ,AMP-Activated Protein Kinases ,Biology ,Biochemistry ,Cell Line ,PIKFYVE ,chemistry.chemical_compound ,Phosphatidylinositol Phosphates ,AMP-activated protein kinase ,Internal medicine ,medicine ,Animals ,Humans ,Insulin ,Phosphorylation ,Rats, Wistar ,Muscle, Skeletal ,Molecular Biology ,Glucose Transporter Type 4 ,Phosphatidylinositol 3-phosphate ,Glucose transporter ,AMPK ,Skeletal muscle ,Opossums ,Cell Biology ,Aminoimidazole Carboxamide ,Rats ,Glucose ,Endocrinology ,medicine.anatomical_structure ,chemistry ,biology.protein ,Phosphatidylinositol 3-Kinase ,GLUT4 ,Muscle Contraction - 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.
- Published
- 2013