We show here that the endogenous sphingosine 1-phosphate 5 receptor (S1P(5), a G protein coupled receptor (GPCR) whose natural ligand is sphingosine 1-phosphate (S1P)) and sphingosine kinases 1 and 2 (SK1 and SK2), which catalyse formation of SIP, are co-localised in the centrosome of mammalian cells, where they may participate in regulating mitosis. The centrosome is a site for active GTP-GDP cycling involving the G-protein, G(i) and tubulin, which are required for spindle pole organization and force generation during cell division. Therefore, the presence of S1P(5) (which normally functions as a plasma membrane guanine nucleotide exchange factor, GEF) and sphingosine kinases in the centrosome might suggest that S1P(5) may function as a ligand activated GEF in regulating G-protein-dependent spindle formation and mitosis. The addition of SIP to cells inhibits trafficking of S1P(5) to the centrosome, suggesting a dynamic shuttling endocytic mechanism controlled by ligand occupancy of cell surface receptor. We therefore propose that the centrosomal S1P(5) receptor might function as an intracellular target of SIP linked to regulation of mitosis.
- sphingosine 1-phosphate
- sphingosine kinase
- sphingosine 1-phosphate receptor 5