Production of phosphatidylinositol 5‐phosphate via PIKfyve and MTMR3 regulates cell migration. (16th November 2012)

• Record Type: Journal Article
• Authors: Oppelt, Angela; Lobert, Viola H; Haglund, Kaisa; Mackey, Ashley M; Rameh, Lucia E; Liestøl, Knut; Oliver Schink, Kay; Marie Pedersen, Nina; Wenzel, Eva M; Haugsten, Ellen M; Brech, Andreas; Erik Rusten, Tor; Stenmark, Harald; Wesche, Jørgen
• Is Part Of: EMBO reports. Volume 14:Number 1(2013)
• Page Start: 57
• Page End: 64
• Publication Date: 2012-11-16
• Subjects: PtdIns5P -- PI3KIII -- MTMR3 -- PIKfyve -- cell migration; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.1038/embor.2012.183
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract : Although phosphatidylinositol 5‐phosphate (PtdIns5 P ) is present in many cell types and its biogenesis is increased by diverse stimuli, its precise cellular function remains elusive. Here we show that PtdIns5 P levels increase when cells are stimulated to move and we find PtdIns5 P to promote cell migration in tissue culture and in a Drosophila in vivo model. First, class III phosphatidylinositol 3‐kinase, which produces PtdIns3 P, was shown to be involved in migration of fibroblasts. In a cell migration screen for proteins containing PtdIns3 P ‐binding motifs, we identified the phosphoinositide 5‐kinase PIKfyve and the phosphoinositide 3‐phosphatase MTMR3, which together constitute a phosphoinositide loop that produces PtdIns5 P via PtdIns(3, 5) P 2 . The ability of PtdIns5 P to stimulate cell migration was demonstrated directly with exogenous PtdIns5 P and a PtdIns5 P ‐producing bacterial enzyme. Thus, the identified phosphoinositide loop defines a new role for PtdIns5 P in cell migration. Production of phosphatidylinositol 5‐phosphate via PIKfyve and MTMR3 regulates cell migration: This study reports that stimulation of cells with FGF1 promotes PtdIns5P production and demonstrates that a PtdIns5 P ‐producing loop constituted by PI3KIII, PIKfyve and MTMR3 is required for cell migration.