Participation of Prostaglandin D2 in the mobilization of the nuclear-localized CTP:phosphocholine cytidylyltransferase alpha in renal epithelial cells

PESCIO LG; STERIN SPEZIALE NB; FAVALE NO; MARQUEZ MG; SANTACREU BJ

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 1861 p. 513 - 523

1388-1981

Phosphatidylcholine (PC) is the main constituent of mammalian cell membranes. Consequently, preservation of membrane PC content and composition ? PC homeostasis ? is crucial to maintain cellular life. PC biosynthetic pathway is generally controlled by CTP:phosphocholine cytidylyltransferase (CCT), which is considered the rate-limiting enzyme. CCTα is an amphitropic protein, whose enzymatic activity is commonly associated with endoplasmic reticulum redistribution. However, most of the enzyme is located inside the nuclei. Here, we dem- onstrate that CCTα is the most abundant isoform in renal collecting duct cells, and its redistribution is dependent on endogenous prostaglandins. Previously we have demonstrated that PC synthesis was inhibited by indometh- acin (Indo) treatment, and this effect was reverted by exogenous PGD2. In this work we found that Indo induced CCTα distribution into intranuclear Lamin A/C foci. Exogenous PGD2 reverted this effect by inducing CCTα redis- tribution to nuclear envelope, suggesting that PGD2 maintains PC synthesis by CCTα mobilization. Interestingly, we found that the effect of PGD2 was dependent on ERK1/2 activation. In conclusion, our previous observations and the present results lead us to suggest that papillary cells possess the ability to maintain their structural integ- rity through the synthesis of their own survival molecule, PGD2, by modulating CCTα intracellular location.