Document Detail

Production of phosphatidylinositol 5-phosphate via PIKfyve and MTMR3 regulates cell migration.
MedLine Citation:
PMID:  23154468     Owner:  NLM     Status:  MEDLINE    
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.
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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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-16
Journal Detail:
Title:  EMBO reports     Volume:  14     ISSN:  1469-3178     ISO Abbreviation:  EMBO Rep.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-06-03     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  100963049     Medline TA:  EMBO Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  57-64     Citation Subset:  IM    
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MeSH Terms
Binding Sites
Cell Line
Cell Movement / physiology*
Class III Phosphatidylinositol 3-Kinases / genetics,  metabolism
Drosophila melanogaster / genetics,  metabolism*
Fibroblasts / cytology,  metabolism*
Gene Expression Regulation
Phosphatidylinositol 3-Kinases / genetics,  metabolism*
Phosphatidylinositol Phosphates / biosynthesis*,  metabolism
Protein Binding
Protein Interaction Domains and Motifs
Protein Tyrosine Phosphatases, Non-Receptor / antagonists & inhibitors,  genetics,  metabolism*
RNA, Small Interfering / genetics
Signal Transduction
Reg. No./Substance:
0/Phosphatidylinositol Phosphates; 0/RNA, Small Interfering; 0/phosphatidylinositol 3,5-diphosphate; 0/phosphatidylinositol 3-phosphate; 0/phosphatidylinositol 5-phosphate; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC III Phosphatidylinositol 3-Kinases; EC protein, human; EC protein, human; EC Tyrosine Phosphatases, Non-Receptor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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