Inhibitory effect of several sphingolipid metabolites on calcineurin. (23rd April 2018)

• Record Type: Journal Article
• Authors: Maruyama, Yoko; Ueno, Satoko; Morita, Mitsuhiro; Hayashi, Fumio; Maekawa, Shohei
• Is Part Of: Neuroscience letters. Volume 673(2018)
• Page Start: 132
• Page End: 135
• Publication Date: 2018-04-23
• Subjects: DRM detergent-resistant membrane microdomain -- CaN calcineurin -- CaM calmodulin -- Cer ceramide -- GluCer glucosulceramide -- GalCer galactosylceramide -- SPC sphingosylphosphorylcholine -- CβG cholesterol β-d-glucoside -- cPA 1-oleoyl-sn-glycero-2, 3-cyclic-phosphate -- LPA lysophosphatidic acid -- LPC lysophophatidylcholine -- SPC sphingosylphosphorylcholine -- S1P sphingosine-1-phosphate -- ARA arachidonic acid -- DHA docosahexaenoic acid -- Psy psychosine (galactosylsphingosine) -- Sph sphingosine -- GlcSph glucosylsphingosine -- solution C 10 mM Tris-HCl, 1 mM MgCl2, 0.2 mM CaCl2, 0.14 M NaCl, pH 7.4 -- TME buffer 10 mM Tris-HCl, 1 mM MgCl2, 0.2 mM EGTA, pH 7.4 -- TMEN buffer TME buffer containing 0.14 M NaCl -- TLC thin layer chromatography; Calcineurin -- Calmodulin -- Sphingosylphosphorylcholine -- Psychosine -- Glucosylsphingosine; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.03.010
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Psychosine, glucosylsphingosine, and sphingosine inhibited calcineurin activity. They showed the effect through binding to calmodulin. Psychosine and glucosylsphingosine showed inhibitory effect on calcineurin B subunit. Abstract: Neurons have well-developed membrane microdomains called "rafts" that are recovered as a detergent-resistant membrane microdomain fraction (DRM). NAP-22 is one of the major protein components of neuronal DRM. In a previous study, we showed that DRM-derived NAP-22 binds ganglioside and the inhibitory effect of ganglioside to calcineurin (CaN), a neuron-enriched calmodulin-regulated phosphoprotein phosphatase. Considering the important roles of CaN in neurons, identification of other cellular regulators of CaN could be a good clue to understand the molecular background of neuronal function. In this study, we screened the effect of several membrane lipid-derived molecules on the CaN activity and found sphingosine and some sphingosine-derived metabolites such as sphingosylphosphorylcholine, galactosylsphingosine (psychosine), and glucosylsphingosine, have inhibitory effect on CaN through the interaction with calmodulin.