Production of phosphatidylinositol 5‐phosphate via PIKfyve and MTMR3 regulates cell migration |
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| Authors: | Angela Oppelt Viola H Lobert Kaisa Haglund Ashley M Mackey Lucia E Rameh Knut Liestøl Kay Oliver Schink Nina Marie Pedersen Eva M Wenzel Ellen M Haugsten Andreas Brech Tor Erik Rusten Harald Stenmark Jørgen Wesche |
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| Affiliation: | 1. Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo;2. Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, , Montebello, N‐0310 Oslo;3. Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, , 7005 Trondheim, Norway;4. Boston Biomedical Research Institute, , Watertown, Massachusetts, 02472 USA;5. Department of Informatics, University of Oslo, , Blindern, N‐0316 Oslo, Norway |
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| 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)P2. 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. |
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| Keywords: | PtdIns5P PI3KIII MTMR3 PIKfyve cell migration |
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