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

Skoug, Cecilia (författare): Lund University,Lunds universitet,Diabetes och hjärnans funktion,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Diabetes and Brain Function,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine

Martinsson, Isak (författare): Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups

Gouras, Gunnar K (författare): Lund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,Experimental Dementia Research,Lund University Research Groups

Meissner, Anja (författare): Lund University,Lunds universitet,Vaskulär biologi,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Vascular Biology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,University of Augsburg

Duarte, João M N (författare): Lund University,Lunds universitet,Diabetes och hjärnans funktion,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,Diabetes and Brain Function,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine

(creator_code:org_t)

2022-07-04
2022
Engelska.
Ingår i: Neurochemical Research. - : Springer Science and Business Media LLC. - 1573-6903 .- 0364-3190. ; 47:10, s. 3114-3125

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Abstract Ämnesord

Stäng

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.

Av författaren/redakt...: Skoug, Cecilia; Martinsson, Isak; Gouras, Gunnar K; Meissner, Anja; Duarte, João M N

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