The sphingosine 1-phosphate receptor 5 and sphingosine kinases 1 and 2 are localised in centrosomes: Possible role in regulating cell division |
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Authors: | Laura Gillies Sue Chin Lee Jaclyn S Long Nicholas Ktistakis Nigel J Pyne Susan Pyne |
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Institution: | 1. Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States;2. Bonfils Blood Center, Denver, CO, United States;3. Surgery, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States;4. Pediatrics, School of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, United States;1. Department of Population Health, New York University School of Medicine, New York, NY, USA;2. Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA;3. Department of Health Studies, The University of Chicago, Chicago, IL, USA;4. The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA;5. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA;6. U-Chicago Research Bangladesh, Ltd., Dhaka, Bangladesh;7. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA;8. Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA;9. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, NY, USA |
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Abstract: | We show here that the endogenous sphingosine 1-phosphate 5 receptor (S1P5, 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, Gi and tubulin, which are required for spindle pole organization and force generation during cell division. Therefore, the presence of S1P5 (which normally functions as a plasma membrane guanine nucleotide exchange factor, GEF) and sphingosine kinases in the centrosome might suggest that S1P5 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 S1P5 to the centrosome, suggesting a dynamic shuttling endocytic mechanism controlled by ligand occupancy of cell surface receptor. We therefore propose that the centrosomal S1P5 receptor might function as an intracellular target of S1P linked to regulation of mitosis. |
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