Adaptation of the secretory pathway to a high secretory demand

IRIS A. GARCÍA; VANINA TORRES DEMICHELIS; LUCIANA SAMPIERI; PABLO DI GIUSTO; CECILIA ALVAREZ

La Serena

Workshop; EMBO WORKSHOP Actualizations in Membrane Trafficking in Health and Disease; 2015

EMBO Molecular Medicine

The secretory pathway is ubiquitous to all mammalian cells and the degree of its extension is cell type-specific, being highly developed in specialized secretory cells. Although the molecular machinery involved in secretion is well studied, how the secretory pathway adapts to respond to a specific stimulus is unclear.Our goal is to determine how cells regulate the adaptation of the secretory pathway in response to high secretory demand. We have used FRTL5 thyroid cell line acutely stimulated with thyroid-stimulating hormone (TSH) as a model to induce expression of thyroid-specific proteins that require the secretory pathway to reach their final destination. Molecular and morphological changes in transport machinery involved in the adaptation to the TSH response were analyzed.Results indicate that TSH stimulation enhances the level of proteins required for membrane transport and ER folding (chaperones) as well as the Golgi volume, in agreement with an increase in thyroid-specific cargo levels. In addition, an increase in CREB3L1, a transcription factor member of the CREB3 family was detected. Interestingly, the kinetics of these TSH-induced changes was similar.Our results indicate that TSH is not only responsible for the synthesis of thyroid hormones, but it also triggers a complete cell response required to cope with the cargo-specific increase and to maintain cellular homeostasis.