Hypertonicity induces lamin A/C synthesis and distribution in a TonEBP/NFAT5 dependent mechanism.

FAVALE NO; STERIN-SPEZIALE NB; FERNANDEZ-TOME MC

Mar del Plata , Buenos Aires, Argentina

Congreso; XLIII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

A-type lamins (lamin A/C) are the most widely studied nucleoskeletal proteins. It has also been shown that lamin A/C is a structural component of nuclear speckles, nucleoplasmic structures enriched in pre-mRNA, splicing and transcription factors, and plays a key role in differentiation process. It has been reported that changes in environmental tonicity induces renal epithelial cell differentiation and that the tonicity-responsive enhancer binding protein (TonEBP/NFAT) regulates gene expression induced by osmotic stress. In the present work we examined how hypertonic medium affects the concentration and nuclear distribution of the lamin A/C in MDCK cells. We also evaluated the relationship between the lamin A/C and TonEBP/NFAT5. Data herein demonstrate that hypertonicity induces lamin A/C increase and nuclear redistribution to nucleoplasmic speckles. Microscopy shows the codistribution of TonEBP/NFAT5 and lamin A/C in nucleoplasmic speckles and immunoprecipitation assays demonstrate the interaction of Lamin A (but not C) withTonEBP/NFAT5. Silencing of TonEBP/NFAT5 causes the redistribution of lamin A/C from speckles to periphery followed by the reduction in lamin A/C levels, thus reflecting that hypertonicity induces lamin A/C specked pattern by a TonEBP-dependent mechanism. We propose that lamin A/C-speckles sequesters TonEBP/NFAT5 thus favoring differentiation process activity.