Sphingosine 1-phosphate receptors modulate intracellular Ca2+ homeostasis.
Ligation of sphingosine 1-phosphate (S1P) to a set of specific receptors named S1P receptors (S1PRs) regulates important biological processes. Although the ability of S1P to increase cytosolic Ca2+ in various cell types is well known, the role of the individual S1PRs has not been fully characterized. Here, we provide a complete analysis of S1P-dependent intracellular Ca2+ homeostasis in HeLa cells. Overexpression of S1P2, or S1P3, but not S1P1, leads to a significant increase in cytosolic and mitochondrial [Ca2+] in response to S1P challenge. Moreover, cells ectopically expressing S1P2, or S1P3 exhibited an appreciable decrease of the free Ca2+ concentration in the endoplasmic reticulum, dependent on stimulation of receptors by S1P endogenously present in the culture medium which was accompanied by a reduced susceptibility to C2-ceramide-induced cell death. These results demonstrate a differential contribution of individual S1PRs to Ca2+ homeostasis and its possible implication in the regulation of cell survival.
Rapizzi
Elena
E
Department of Biochemical Sciences, Istituto Interuniversitario di Miologia (IIM), University of Firenze, 44100 Firenze, Italy.
Donati
Chiara
C
Cencetti
Francesca
F
Pinton
Paolo
P
Rizzuto
Rosario
R
Bruni
Paola
P
D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*
D049349:Receptors, Lysosphingolipid; D002118:Calcium