The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity
| Autor: | Kempf, Anissa, Tews, Bjoern, Arzt, Michael E., Weinmann, Oliver, Obermair, Franz J., Pernet, Vincent, Zagrebelsky, Marta, Delekate, Andrea, Iobbi, Cristina, Zemmar, Ajmal, Ristic, Zorica, Gullo, Miriam, Spies, Peter, Dodd, Dana, Gygax, Daniel, Korte, Martin, Schwab, Martin E. |
|---|---|
| Přispěvatelé: | University of Zurich |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
rho GTP-Binding Proteins
QH301-705.5 Nogo Proteins Lipoproteins Long-Term Potentiation 610 Medicine & health 1100 General Agricultural and Biological Sciences GTP-Binding Protein alpha Subunits G12-G13 Hippocampus Biochemistry Mice Developmental Neuroscience Sphingosine 1300 General Biochemistry Genetics and Molecular Biology 2400 General Immunology and Microbiology Neurobiology of Disease and Regeneration mental disorders Neurites Animals Biology (General) Sphingosine-1-Phosphate Receptors Biology Myelin Sheath Cell Proliferation Lipoprotein Receptors Mice Knockout Neuronal Plasticity 10242 Brain Research Institute Serine Endopeptidases Motor Cortex Proteins 2800 General Neuroscience Neurochemistry Receptors Lysosphingolipid Gene Expression Regulation Synapses 570 Life sciences biology Proprotein Convertases Lysophospholipids rhoA GTP-Binding Protein Myelin Proteins psychological phenomena and processes Signal Transduction Research Article Synaptic Plasticity Neuroscience |
| Zdroj: | PLoS Biology, Vol 12, Iss 1, p e1001763 (2014) PLoS Biology, 12 (1) PLoS Biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | Nogo-A is a membrane protein of the central nervous system (CNS) restricting neurite growth and synaptic plasticity via two extracellular domains: Nogo-66 and Nogo-A-Δ20. Receptors transducing Nogo-A-Δ20 signaling remained elusive so far. Here we identify the G protein-coupled receptor (GPCR) sphingosine 1-phosphate receptor 2 (S1PR2) as a Nogo-A-Δ20-specific receptor. Nogo-A-Δ20 binds S1PR2 on sites distinct from the pocket of the sphingolipid sphingosine 1-phosphate (S1P) and signals via the G protein G13, the Rho GEF LARG, and RhoA. Deleting or blocking S1PR2 counteracts Nogo-A-Δ20- and myelin-mediated inhibition of neurite outgrowth and cell spreading. Blockade of S1PR2 strongly enhances long-term potentiation (LTP) in the hippocampus of wild-type but not Nogo-A−/− mice, indicating a repressor function of the Nogo-A/S1PR2 axis in synaptic plasticity. A similar increase in LTP was also observed in the motor cortex after S1PR2 blockade. We propose a novel signaling model in which a GPCR functions as a receptor for two structurally unrelated ligands, a membrane protein and a sphingolipid. Elucidating Nogo-A/S1PR2 signaling platforms will provide new insights into regulation of synaptic plasticity. PLoS Biology, 12 (1) ISSN:1544-9173 ISSN:1545-7885 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|