The correct localization of PTEN in epithelial cells depends on glycosphingolipid metabolism.

PESCIO LG; STERIN-SPEZIALE NB; ROMERO DJ; TULINO MS

Cordoba

Congreso; SAIB 2016; 2016

We have previously demonstrated that MDCK cells develop a polarized phenotype when they are subjected to hypertonic medium, and we found that glycosphingolipid synthesis is essential in this process. Polarized cells show two separated membrane domains, apical and basolateral, with different protein and lipid composition. The localization of PTEN, a key enzyme in the metabolism of the polyphosphoinositides, is important in the polarity of epithelial cells. In this study we analyzed the distribution of PTEN in MDCK cells in different experimental conditions. We found that non-differentiated cells cultured under isotonicity showed cytoplasmic localization of PTEN, but when the cells were subjected to hypertonicity developed a mature membrane with apical accumulation of the apical marker gp135 and PTEN concentrated in this membrane domain with a dot ? like distribution. Interestingly, when the cells were incubated under hypertonicity in the presence of D-PDMP, an inhibitor of glucosylceramide synthase, cells did not develop the polarized phenotype and PTEN was drastically misslocalized. We previously showed that hypertonicity induces an increase in glucosylceramide synthesis. These results suggest that glycosphingolipids are necessary for the correct localization of PTEN and indicate an important crosstalk between sphingolipid and polyphosphoinositides metabolism.