SPHINGOSINE KINASE 2 COORDINATES THE DISASSEMBLY OF CELL JUNCTIONS DURING CELL EXTRUSION

PESCIO LG; TARALLO E; SANTACREU BJ; CHAVEZ FLORES JC; FAVALE NO; ROMERO DJ; STERIN SPEZIALE N

Entre Ríos

Congreso; SAIB 2018; 2018

SAIB

The maintenance of the epithelial integrity is essential to prevent inflammation, inappropriate growth factor signaling, and invasion by pathogens. Epithelial integrity requires a high cell turnover given by coordination between cell division and cell extrusion. Cell extrusion acts as key regulator of cell density homeostasis by removing the cells and preserving tissue integrity. This process is triggered by the release of sphingosine-1-phosphate (S1P) which activate S1P receptor 2 and produces the contraction of an actomyosin ring in the neighboring cell. The contraction squeezes the cell out apically while drawing together neighboring cells and preventing any gaps to the epithelial barrier. Previously, we demonstrated that cell extrusion is triggered by sphingosine kinase 2 (SK2) in differentiated MDCK cells. The goal of this work was to study the implication of SK2/S1P pathway in the disassembly of cell junctions that occurs as a mandatory process before cell extrusion. For this end, differentiated MDCK cells were subjected to SK inhibitors or knocked down for SK2. After incubation, focal adhesion (talin and vimculin) and adherens junction (E-cadherin and β-catenin) proteins were visualized by fluorescence microscopy in extruding cells. We found that SK2 participates in the disassembly of cell-cell and cell-matrix junction. Moreover, we found that the inhibition of SK2 impairs the degradation of E- cadherin. These results show that SK2 / S1P pathway besides activating the process in neighboring cells also has an effect on the extruded cell itself, regulating in a global and coordinated manner the entire cell extrusion process.