title: The sphingosine 1-phosphate receptor 5 and sphingosine kinases 1 and 2 are localised in centrosomes: possible role in regulating cell division.
abstract: 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 S1P, 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 S1P 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 S1P linked to regulation of mitosis.
authors.affiliation: Cell Biology Group, SIPBS, University of Strathclyde, 27 Taylor St, Glasgow, G4 0NR, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Gillies
authors.forename: Sue Chin
authors.initials: SC
authors.lastname: Lee
authors.forename: Jaclyn S
authors.initials: JS
authors.lastname: Long
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ktistakis
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Pyne
authors.forename: Susan
authors.initials: S
authors.lastname: Pyne
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D018385:Centrosome / Q000201:enzymology / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000494:pharmacology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D008938:Mitosis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000099157:Sphingosine Kinase
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D034741:RNA, Small Interfering; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate