Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration.

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
EMBO Rep. 2013 14 (1): 57-64

PMID: 23154468 · PMCID: PMC3537138 · DOI:10.1038/embor.2012.183

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.

MeSH Terms (16)

Animals Binding Sites Cell Line Cell Movement Class III Phosphatidylinositol 3-Kinases Drosophila melanogaster Fibroblasts Gene Expression Regulation Humans Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates Protein Binding Protein Interaction Domains and Motifs Protein Tyrosine Phosphatases, Non-Receptor RNA, Small Interfering Signal Transduction

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