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Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture

Skoug, Cecilia LU ; Martinsson, Isak LU ; Gouras, Gunnar K LU orcid ; Meissner, Anja LU orcid and Duarte, João M N LU orcid (2022) In Neurochemical Research 47(10). p.3114-3125
Abstract

Sphingosine-1-phosphate (S1P) is best known for its roles as vascular and immune regulator. Besides, it is also present in the central nervous system (CNS) where it can act as neuromodulator via five S1P receptors (S1PRs), and thus control neurotransmitter release. The distribution of S1PRs in the active zone and postsynaptic density of CNS synapses remains unknown. In the current study, we investigated the localization of S1PR1-5 in synapses of the mouse cortex. Cortical nerve terminals purified in a sucrose gradient were endowed with all five S1PRs. Further subcellular fractionation of cortical nerve terminals revealed S1PR2 and S1PR4 immunoreactivity in the active zone of presynaptic nerve terminals. Interestingly, only S1PR2 and... (More)

Sphingosine-1-phosphate (S1P) is best known for its roles as vascular and immune regulator. Besides, it is also present in the central nervous system (CNS) where it can act as neuromodulator via five S1P receptors (S1PRs), and thus control neurotransmitter release. The distribution of S1PRs in the active zone and postsynaptic density of CNS synapses remains unknown. In the current study, we investigated the localization of S1PR1-5 in synapses of the mouse cortex. Cortical nerve terminals purified in a sucrose gradient were endowed with all five S1PRs. Further subcellular fractionation of cortical nerve terminals revealed S1PR2 and S1PR4 immunoreactivity in the active zone of presynaptic nerve terminals. Interestingly, only S1PR2 and S1PR3 immunoreactivity was found in the postsynaptic density. All receptors were present outside the active zone of nerve terminals. Neurons in the mouse cortex and primary neurons in culture showed immunoreactivity against all five S1PRs, and Ca 2+ imaging revealed that S1P inhibits spontaneous neuronal activity in a dose-dependent fashion. When testing selective agonists for each of the receptors, we found that only S1PR1, S1PR2 and S1PR4 control spontaneous neuronal activity. We conclude that S1PR2 and S1PR4 are located in the active zone of nerve terminals and inhibit neuronal activity. Future studies need to test whether these receptors modulate stimulation-induced neurotransmitter release.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neurochemical Research
volume
47
issue
10
pages
3114 - 3125
publisher
Springer
external identifiers
  • scopus:85133307155
  • pmid:35781853
ISSN
1573-6903
DOI
10.1007/s11064-022-03664-3
language
English
LU publication?
yes
additional info
© 2022. The Author(s).
id
b947739d-90e1-465f-826c-43ca699b8cbb
date added to LUP
2022-07-10 13:17:08
date last changed
2025-03-06 05:31:54
@article{b947739d-90e1-465f-826c-43ca699b8cbb,
  abstract     = {{<p>Sphingosine-1-phosphate (S1P) is best known for its roles as vascular and immune regulator. Besides, it is also present in the central nervous system (CNS) where it can act as neuromodulator via five S1P receptors (S1PRs), and thus control neurotransmitter release. The distribution of S1PRs in the active zone and postsynaptic density of CNS synapses remains unknown. In the current study, we investigated the localization of S1PR1-5 in synapses of the mouse cortex. Cortical nerve terminals purified in a sucrose gradient were endowed with all five S1PRs. Further subcellular fractionation of cortical nerve terminals revealed S1PR2 and S1PR4 immunoreactivity in the active zone of presynaptic nerve terminals. Interestingly, only S1PR2 and S1PR3 immunoreactivity was found in the postsynaptic density. All receptors were present outside the active zone of nerve terminals. Neurons in the mouse cortex and primary neurons in culture showed immunoreactivity against all five S1PRs, and Ca 2+ imaging revealed that S1P inhibits spontaneous neuronal activity in a dose-dependent fashion. When testing selective agonists for each of the receptors, we found that only S1PR1, S1PR2 and S1PR4 control spontaneous neuronal activity. We conclude that S1PR2 and S1PR4 are located in the active zone of nerve terminals and inhibit neuronal activity. Future studies need to test whether these receptors modulate stimulation-induced neurotransmitter release. </p>}},
  author       = {{Skoug, Cecilia and Martinsson, Isak and Gouras, Gunnar K and Meissner, Anja and Duarte, João M N}},
  issn         = {{1573-6903}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{10}},
  pages        = {{3114--3125}},
  publisher    = {{Springer}},
  series       = {{Neurochemical Research}},
  title        = {{Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture}},
  url          = {{http://dx.doi.org/10.1007/s11064-022-03664-3}},
  doi          = {{10.1007/s11064-022-03664-3}},
  volume       = {{47}},
  year         = {{2022}},
}