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Molecular and cellular changes of membrane transport machinery in response to a secretory stimulus García I.A.; Martinez H.; Sampieri L.; and Alvarez, C.I. Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET). Facultad de Ciencias Químicas. UNC. Córdoba-Argentina. agarcia@fcq.unc.edu.ar. Introduction: The secretory pathway is involved in transport of proteins (and lipids) to the plasma membrane, the extracellular environment, and to membrane-bound compartments that participate in different membrane traffic events. Although the molecular machinery involved in this pathway is well studied, the mechanisms that regulate the cellular adaptation to a higher secretory demand are not clearly understood. Our work aims to analyze molecular and cellular mechanisms that are involved in the adaptation to a secretory stimulus. Material and Methods: The FRTL-5 thyroid cell line was used as a secretory model. In these cells, secretory activity is induced by thyroid stimulating hormone (TSH) which stimulates the synthesis of cell specific proteins that require the secretory pathway to reach their final destination. Analysis were performed comparing cells grown in basal (-TSH) or stimulated (+TSH) condition. Results: Our results show that TSH stimulation also raises the level of proteins required for transport and chaperones involved in ER folding. In agreement, an increase in their mRNA levels was detected. Moreover, Golgi volume also increases. Time course analysis of the TSH response showed a simultaneous increase of membrane transport proteins, ER chaperones and specific thyroid cargo. Discussion: FRTL-5 provides a physiological model of cell adaptation to a secretory demand. Our data indicate that, to maintain cellular homeostasis after TSH stimulation, a global cell response is induced to cope with cargo increase, suggesting that common signaling pathways are able to modulate specific secretory activity and traffic-related genes.