The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity.
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) sphing...
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doaj-bf0435eb427c4707b9e3fffb96f095d42021-07-02T15:13:56ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852014-01-01121e100176310.1371/journal.pbio.1001763The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity.Anissa KempfBjoern TewsMichael E ArztOliver WeinmannFranz J ObermairVincent PernetMarta ZagrebelskyAndrea DelekateCristina IobbiAjmal ZemmarZorica RisticMiriam GulloPeter SpiesDana DoddDaniel GygaxMartin KorteMartin E SchwabNogo-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.http://europepmc.org/articles/PMC3891622?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anissa Kempf Bjoern Tews Michael E Arzt Oliver Weinmann Franz J Obermair Vincent Pernet Marta Zagrebelsky Andrea Delekate Cristina Iobbi Ajmal Zemmar Zorica Ristic Miriam Gullo Peter Spies Dana Dodd Daniel Gygax Martin Korte Martin E Schwab |
spellingShingle |
Anissa Kempf Bjoern Tews Michael E Arzt Oliver Weinmann Franz J Obermair Vincent Pernet Marta Zagrebelsky Andrea Delekate Cristina Iobbi Ajmal Zemmar Zorica Ristic Miriam Gullo Peter Spies Dana Dodd Daniel Gygax Martin Korte Martin E Schwab The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. PLoS Biology |
author_facet |
Anissa Kempf Bjoern Tews Michael E Arzt Oliver Weinmann Franz J Obermair Vincent Pernet Marta Zagrebelsky Andrea Delekate Cristina Iobbi Ajmal Zemmar Zorica Ristic Miriam Gullo Peter Spies Dana Dodd Daniel Gygax Martin Korte Martin E Schwab |
author_sort |
Anissa Kempf |
title |
The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. |
title_short |
The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. |
title_full |
The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. |
title_fullStr |
The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. |
title_full_unstemmed |
The sphingolipid receptor S1PR2 is a receptor for Nogo-a repressing synaptic plasticity. |
title_sort |
sphingolipid receptor s1pr2 is a receptor for nogo-a repressing synaptic plasticity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Biology |
issn |
1544-9173 1545-7885 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3891622?pdf=render |
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