RRC ID 21808
Author Oppelt A, Lobert VH, Haglund K, Mackey AM, Rameh LE, Liestøl K, Schink KO, Pedersen NM, Wenzel EM, Haugsten EM, Brech A, Rusten TE, Stenmark H, Wesche J.
Title Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration.
Journal EMBO Rep.
Abstract Although phosphatidylinositol 5-phosphate (PtdIns5P) is present in many cell types and its biogenesis is increased by diverse stimuli, its precise cellular function remains elusive. Here we show that PtdIns5P levels increase when cells are stimulated to move and we find PtdIns5P to promote cell migration in tissue culture and in a Drosophila in vivo model. First, class III phosphatidylinositol 3-kinase, which produces PtdIns3P, was shown to be involved in migration of fibroblasts. In a cell migration screen for proteins containing PtdIns3P-binding motifs, we identified the phosphoinositide 5-kinase PIKfyve and the phosphoinositide 3-phosphatase MTMR3, which together constitute a phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P(2). The ability of PtdIns5P to stimulate cell migration was demonstrated directly with exogenous PtdIns5P and a PtdIns5P-producing bacterial enzyme. Thus, the identified phosphoinositide loop defines a new role for PtdIns5P in cell migration.
Volume 14(1)
Pages 57-64
Published 2013-1
DOI 10.1038/embor.2012.183
PII embor2012183
PMID 23154468
PMC PMC3537138
MeSH Animals Binding Sites Cell Line Cell Movement / physiology* Class III Phosphatidylinositol 3-Kinases / genetics Class III Phosphatidylinositol 3-Kinases / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Fibroblasts / cytology Fibroblasts / metabolism* Gene Expression Regulation Humans Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism* Phosphatidylinositol Phosphates / biosynthesis* Phosphatidylinositol Phosphates / metabolism Protein Binding Protein Interaction Domains and Motifs Protein Tyrosine Phosphatases, Non-Receptor / antagonists & inhibitors Protein Tyrosine Phosphatases, Non-Receptor / genetics Protein Tyrosine Phosphatases, Non-Receptor / metabolism* RNA, Small Interfering / genetics Signal Transduction
IF 8.383
Times Cited 23