Subcellular localization of sphingosine 1-phosphate receptors in synapses of the mouse cortex
Skoug, Cecilia LU ; Meissner, Anja LU and Duarte, Joao LU
(2019)
ISN‐ASN 2019 Meeting, Montreal, Canada
p.79-79
- Abstract
- Sphingosine 1-phosphate (S1P) has pleiotropic biological functions in the regulation of proliferation, survival, migration, inflammation or angiogenesis. S1P acts as intracellular second messenger,
as well as extracellular receptor ligand via five G-protein coupled
receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation or apoptosis, excitatory neurotransmission and neuroglia
activation, and S1P metabolism alterations have been associated to
neurodegenerative disorders. Interestingly, an agonist targeting
S1PR1,3,4,5 (FTY720) shows neuroprotective properties through
mechanisms that are not fully unveiled, but might include the
control of neuroinflammation, vascular deterioration and synaptic
... (More) - Sphingosine 1-phosphate (S1P) has pleiotropic biological functions in the regulation of proliferation, survival, migration, inflammation or angiogenesis. S1P acts as intracellular second messenger,
as well as extracellular receptor ligand via five G-protein coupled
receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation or apoptosis, excitatory neurotransmission and neuroglia
activation, and S1P metabolism alterations have been associated to
neurodegenerative disorders. Interestingly, an agonist targeting
S1PR1,3,4,5 (FTY720) shows neuroprotective properties through
mechanisms that are not fully unveiled, but might include the
control of neuroinflammation, vascular deterioration and synaptic
dysfunction. The subcellular distribution of S1PRs in nerve
terminals is hitherto unknown. The present study aimed at
determining the synaptic localisation of S1PRs in the cortex of
adult male mice. Synaptosomes were purified from mouse cortex
homogenates using a sucrose density gradient centrifugation, and
further fractioned into pre-, post- and extrasynaptic zones using a
series of pH shifts that allow successive solubilisation of synaptic
components (Phillips et al., Neuron 32:63, 2001). Western blot
analysis of the obtained fractions, as well as total protein extracts
from cortex revealed that S1PR1 is present in similar amounts in
total extracts, synaptosomes and the extrasynaptic fraction, but
absent from the pre- and postsynaptic fractions. S1PR2 was
ubiquitously distributed, showing 3-fold higher levels in the
presynaptic zone than the post- (P<0.05) and extrasynaptic
(P<0.05) fractions. Similarly, S1PR4 was also distributed across
all synaptic fractions but 4-fold more enriched presynaptically.
S1PR3 and S1PR5 were not efficiently detected by immunoblotting
in synaptosomes and synaptic fractions. Altogether, these results
point towards S1PR2 and S1PR4 being particularly well poised to
directly modulate synaptic transmission and plasticity upon S1P
activation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/919b00f7-e5fa-4ca4-b284-b9ab5bde5b7d
- author
- Skoug, Cecilia
LU
; Meissner, Anja
LU
and Duarte, Joao
LU
- organization
- publishing date
- 2019
- type
- Contribution to conference
- publication status
- published
- subject
- pages
- 79 - 79
- conference name
- ISN‐ASN 2019 Meeting, Montreal, Canada
- conference dates
- 2019-08-04 - 2019-08-08
- language
- English
- LU publication?
- yes
- id
- 919b00f7-e5fa-4ca4-b284-b9ab5bde5b7d
- alternative location
- http://www.isnplaza.org/isn/program_and_abstractbook/ISN2019/PDF-Versions/ISN-ASN%202019%20Program%20&%20Abstract%20Book.pdf
- date added to LUP
- 2021-09-21 19:18:24
- date last changed
- 2021-09-24 13:44:15
@misc{919b00f7-e5fa-4ca4-b284-b9ab5bde5b7d,
abstract = {{Sphingosine 1-phosphate (S1P) has pleiotropic biological functions in the regulation of proliferation, survival, migration, inflammation or angiogenesis. S1P acts as intracellular second messenger,<br>
as well as extracellular receptor ligand via five G-protein coupled<br>
receptors (S1PR1-5). In the brain, S1P regulates neuronal proliferation or apoptosis, excitatory neurotransmission and neuroglia<br>
activation, and S1P metabolism alterations have been associated to<br>
neurodegenerative disorders. Interestingly, an agonist targeting<br>
S1PR1,3,4,5 (FTY720) shows neuroprotective properties through<br>
mechanisms that are not fully unveiled, but might include the<br>
control of neuroinflammation, vascular deterioration and synaptic<br>
dysfunction. The subcellular distribution of S1PRs in nerve<br>
terminals is hitherto unknown. The present study aimed at<br>
determining the synaptic localisation of S1PRs in the cortex of<br>
adult male mice. Synaptosomes were purified from mouse cortex<br>
homogenates using a sucrose density gradient centrifugation, and<br>
further fractioned into pre-, post- and extrasynaptic zones using a<br>
series of pH shifts that allow successive solubilisation of synaptic<br>
components (Phillips et al., Neuron 32:63, 2001). Western blot<br>
analysis of the obtained fractions, as well as total protein extracts<br>
from cortex revealed that S1PR1 is present in similar amounts in<br>
total extracts, synaptosomes and the extrasynaptic fraction, but<br>
absent from the pre- and postsynaptic fractions. S1PR2 was<br>
ubiquitously distributed, showing 3-fold higher levels in the<br>
presynaptic zone than the post- (P<0.05) and extrasynaptic<br>
(P<0.05) fractions. Similarly, S1PR4 was also distributed across<br>
all synaptic fractions but 4-fold more enriched presynaptically.<br>
S1PR3 and S1PR5 were not efficiently detected by immunoblotting<br>
in synaptosomes and synaptic fractions. Altogether, these results<br>
point towards S1PR2 and S1PR4 being particularly well poised to<br>
directly modulate synaptic transmission and plasticity upon S1P<br>
activation.}},
author = {{Skoug, Cecilia and Meissner, Anja and Duarte, Joao}},
language = {{eng}},
pages = {{79--79}},
title = {{Subcellular localization of sphingosine 1-phosphate receptors in synapses of the mouse cortex}},
url = {{http://www.isnplaza.org/isn/program_and_abstractbook/ISN2019/PDF-Versions/ISN-ASN%202019%20Program%20&%20Abstract%20Book.pdf}},
year = {{2019}},
}