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Joao Duarte

Research team manager

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


  • Cecilia Skoug
  • Isak Martinsson
  • Gunnar K Gouras
  • Anja Meissner
  • João M N Duarte

Summary, in English

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.


  • MultiPark: Multidisciplinary research focused on Parkinson´s disease
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes and Brain Function
  • WCMM-Wallenberg Centre for Molecular Medicine
  • Experimental Dementia Research
  • Vascular Biology

Publishing year







Neurochemical Research





Document type

Journal article




  • Inorganic Chemistry
  • Neurosciences
  • Physiology



Research group

  • Diabetes and Brain Function
  • Experimental Dementia Research
  • Vascular Biology


  • ISSN: 1573-6903