ADAPTATION MECHANISMS REGULATING THE SECRETORY PATHWAY IN RESPONSE TO A SECRETORY STIMULUS.

TORRES DEMICHELIS, VA; SAMPIERI, L; ALVAREZ, C

Córdoba

Congreso; SAIB 2016; 2016

Our work aims to analyze molecular and cellular mechanisms that are involved in the adaptation of the secretory pathway to a higher secretory demand. Rat thyroid cells (FRTL5) were used as a secretory model. FRTL5 are stimulated with thyroid-stimulating hormone (TSH) to induce expression of thyroid-specific cargo proteins [ex: sodium iodide symporter (NIS)] that require the secretory pathway to reach their final destination. Moreover, TSH increases the expression of sterol regulatory element-binding proteins (SREBP1c and SREBP-2), master transcriptional regulators of cholesterol and fatty acid synthesis. We have showed (SAIB 2014) that TSH stimulation enhances the level of proteins required for membrane transport as well as the Golgi volume. We now show that inhibition of SREBPs activity, induced by 25-HC cholesterol, modifies the increase in level of proteins required for membrane transport induced by TSH. Also, overexpression of CREB3L1 regulates expression of SREBP1c. Our data suggest that TSH-activated pathways coordinately synchronize the expression of lipids and transport factors necessary to amplify the structure and function of the secretory pathway.