title: AMP-activated protein kinase induces actin cytoskeleton reorganization in epithelial cells.
abstract: AMP-activated protein kinase (AMPK), a known regulator of cellular and systemic energy balance, is now recognized to control cell division, cell polarity and cell migration, all of which depend on the actin cytoskeleton. Here we report the effects of A769662, a pharmacological activator of AMPK, on cytoskeletal organization and signalling in epithelial Madin-Darby canine kidney (MDCK) cells. We show that AMPK activation induced shortening or radiation of stress fibers, uncoupling from paxillin and predominance of cortical F-actin. In parallel, Rho-kinase downstream targets, namely myosin regulatory light chain and cofilin, were phosphorylated. These effects resembled the morphological changes in MDCK cells exposed to hyperosmotic shock, which led to Ca(2+)-dependent AMPK activation via calmodulin-dependent protein kinase kinase-beta(CaMKKbeta), a known upstream kinase of AMPK. Indeed, hypertonicity-induced AMPK activation was markedly reduced by the STO-609 CaMKKbeta inhibitor, as was the increase in MLC and cofilin phosphorylation. We suggest that AMPK links osmotic stress to the reorganization of the actin cytoskeleton.
authors.affiliation: de Duve Institute, Université catholique de Louvain, Avenue Hippocrate, B-1200 Brussels, Belgium.
authors.forename: Lisa
authors.initials: L
authors.lastname: Miranda
authors.forename: Sarah
authors.initials: S
authors.lastname: Carpentier
authors.forename: Anna
authors.initials: A
authors.lastname: Platek
authors.forename: Nusrat
authors.initials: N
authors.lastname: Hussain
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Gueuning
authors.forename: Didier
authors.initials: D
authors.lastname: Vertommen
authors.forename: Yurda
authors.initials: Y
authors.lastname: Ozkan
authors.forename: Brice
authors.initials: B
authors.lastname: Sid
authors.forename: Louis
authors.initials: L
authors.lastname: Hue
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rider
authors.forename: Sandrine
authors.initials: S
authors.lastname: Horman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D053644:Naphthalimides / Q000494:pharmacology; D009997:Osmotic Pressure; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D011753:Pyrones / Q000494:pharmacology; D012265:Ribonucleotides / Q000494:pharmacology; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D053644:Naphthalimides; D051419:Paxillin; D011753:Pyrones; D012265:Ribonucleotides; C458525:STO 609; D012462:Saline Solution, Hypertonic; D013876:Thiophenes; D000620:Aminoimidazole Carboxamide; D054460:rho-Associated Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile