Hypertonicity Induces Lamin A/C Synthesis and Distribution In A Tonebp/Nfat5 Dependent Mechanism.

NICOLÁS O. FAVALE; NORMA B. STERIN-SPEZIALE; MARÍA C. FERNÁNDEZ TOME

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Bioquímica y Biología Molecular; 2007

SAIB

CB-C12.HYPERTONICITY INDUCES LAMIN A/C SYNTHESISAND DISTRIBUTION IN A TONEBP/NFAT5 DEPENDENTMECHANISMFavale NO, Sterin-Speziale NB, Fernandez-Tome MC.Biología Celular, FFYB-UBA, IQUIFIB-CONICET, Buenos Aires,Argentina. E-mail: nofaval@ffyb.uba.arA-type lamins (lamin A/C) are the most widely studiednucleoskeletal proteins. It has also been shown that lamin A/C is astructural component of nuclear speckles, nucleoplasmic structuresenriched in pre-mRNA, splicing and transcription factors, and playsa key role in differentiation process. It has been reported thatchanges in environmental tonicity induces renal epithelial celldifferentiation and that the tonicity-responsive enhancer bindingprotein (TonEBP/NFAT) regulates gene expression induced byosmotic stress. In the present work we examined how hypertonicmedium affects the concentration and nuclear distribution of thelamin A/C in MDCK cells. We also evaluated the relationshipbetween the lamin A/C and TonEBP/NFAT5. Data hereindemonstrate that hypertonicity induces lamin A/C increase andnuclear redistribution to nucleoplasmic speckles. Microscopyshows the codistribution of TonEBP/NFAT5 and lamin A/C innucleoplasmic speckles and immunoprecipitation assaysdemonstrate the interaction of Lamin A (but not C) withTonEBP/NFAT5. Silencing of TonEBP/NFAT5 causes theredistribution of lamin A/C from speckles to periphery followed bythe reduction in lamin A/C levels, thus reflecting that hypertonicityinduces lamin A/C specked pattern by a TonEBP-dependentmechanism. We propose that lamin A/C-speckles sequestersTonEBP/NFAT5 thus favoring differentiation process activity.