ROLE OF SPHINGOSINE-1-PHOSPHATE RECEPTOR 3 IN EPITHELIAL CELL DIFFERENTIATION

ROMERO, DJ; FAVALE, NO; SANTACREU, BJ; TARALLO, E; PESCIO, LG

Salta

Congreso; 55th Annual Meeting Argentine Society for Biochemistry and Molceular Biology; 2019

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Madin-Darby canine kidney cells (MDCK) acquired a differentiated phenotype when they are cultured in hypertonic medium. Previous works from our lab have demonstrated that sphingolipid metabolism is involved in such differentiation process. One of the most active sphingolipid issphingosine-1-phosphate (S1P), that has been classically associated with the induction of a proliferative phenotype and anti-apoptotic activity. However, the participation of S1P in cell differentiation is not well understood. S1P can act both intracellularly as second messenger and extracellularly as ligand for cell surface receptors (S1PRs). We have reported that S1P levels decreases during transition to the differentiated state and S1P acts by its receptors. In this work we evaluated whether changes in the expression and/or localization of S1PRs are involved in thedifferentiation process. Immunofluorescence studies showed that during cell differentiation S1PR3 was located in intracellular vesicles. However, S1PR3-vecicles changed their intracellular localization depending on cell differentiation state. In proliferative state S1PR3 was in all the cytoplasm, but was relocated to sub-apical distribution during differentiation process. At the final stage of cellular differentiation, where apical domain and primary cilium were present, S1PR3-vecicles signal decreased. Moreover, pharmacological inhibition of S1PR3 accelerated the apical membrane establishment. These results suggest that S1PR3 need to be inactivated/degraded for final epithelial cell differentiation, which propose a possible new function for the S1P/S1PR3 pathway in phenotypical epithelial cell differentiation.