Memo has a novel role in S1P signaling and is [corrected] crucial for vascular development

Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one Vol. 9; no. 4; p. e94114
Main Authors:	Kondo, Shunya, Bottos, Alessia, Allegood, Jeremy C, Masson, Regis, Maurer, Francisca G, Genoud, Christel, Kaeser, Patrick, Huwiler, Andrea, Murakami, Masato, Spiegel, Sarah, Hynes, Nancy E
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01-04-2014 Public Library of Science (PLoS)
Subjects:	Analysis Angiogenesis Animals Apoptosis Apoptosis - physiology Autocrine signalling Biochemistry Biology and Life Sciences Biomedical research Bleeding Cadherins Cell activation Cell adhesion & migration Cell migration Cell Movement - physiology Cell Proliferation - physiology Cell survival Defects Embryo fibroblasts Embryogenesis Embryonic growth stage Embryos Endothelial cells Fibroblasts Growth factors Kinases Lymphocytes Lysophospholipids - genetics Lysophospholipids - metabolism Mice Mice, Knockout Molecular biology Motility Neovascularization, Physiologic - physiology Nonheme Iron Proteins - genetics Nonheme Iron Proteins - metabolism Paracrine signalling Phosphates Phospholipids Phosphotransferases (Alcohol Group Acceptor) - metabolism Physiology Platelet-derived growth factor Protein binding Protein-tyrosine kinase receptors Proteins Receptor mechanisms Receptors Rodents Signal transduction Signal Transduction - physiology Sphingosine Sphingosine - analogs & derivatives Sphingosine - genetics Sphingosine - metabolism Sphingosine 1-phosphate Starvation Survival Tyrosine United States > US Virginia Switzerland
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Memo is a conserved protein that was identified as an essential mediator of tumor cell motility induced by receptor tyrosine kinase activation. Here we show that Memo null mouse embryonic fibroblasts (MEFs) are impaired in PDGF-induced migration and this is due to a defect in sphingosine-1-phosphate (S1P) signaling. S1P is a bioactive phospholipid produced in response to multiple stimuli, which regulates many cellular processes. S1P is secreted to the extracellular milieu where it exerts its function by binding a family of G-protein coupled receptors (S1PRs), causing their activation in an autocrine or paracrine manner. The process, termed cell-autonomous S1PR signaling, plays a role in survival and migration. Indeed, PDGF uses cell-autonomous S1PR signaling to promote cell migration; we show here that this S1P pathway requires Memo. Using vascular endothelial cells (HUVECs) with Memo knock-down we show that their survival in conditions of serum-starvation is impaired. Furthermore, Memo loss in HUVECs causes a reduction of junctional VE-cadherin and an increase in sprout formation. Each of these phenotypes is rescued by S1P or S1P agonist addition, showing that Memo also plays an important role in cell-autonomous S1PR signaling in endothelial cells. We also produced conventional and endothelial cell-specific conditional Memo knock-out mouse strains and show that Memo is essential for embryonic development. Starting at E13.5 embryos of both strains display bleeding and other vascular problems, some of the phenotypes that have been described in mouse strains lacking S1PRs. The essential role of Memo in embryonic vascular development may be due in part to alterations in S1P signaling. Taken together our results show that Memo has a novel role in the S1P pathway and that Memo is needed to promote cell-autonomous S1PR activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: One of the authors (Masato Murakami) has the affiliation to a commercial company (Novartis Institutes for Biomedical Research). The authors declare that this does not alter their adherence to all the PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: SK NH. Performed the experiments: SK AB JA RM FM PK. Analyzed the data: SK AB JA CG MM SS. Contributed reagents/materials/analysis tools: SK JA AH SS. Wrote the paper: SK AB NH.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0094114