CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells

CREB3L1 介导激素刺激甲状腺细胞分泌途径的功能和结构适应

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作者:Iris A García, Vanina Torres Demichelis, Diego L Viale, Pablo Di Giusto, Yulia Ezhova, Roman S Polishchuk, Luciana Sampieri, Hernán Martinez, Elizabeth Sztul, Cecilia Alvarez

Abstract

Many secretory cells increase the synthesis and secretion of cargo proteins in response to specific stimuli. How cells couple increased cargo load with a coordinate rise in secretory capacity to ensure efficient transport is not well understood. We used thyroid cells stimulated with thyrotropin (TSH) to demonstrate a coordinate increase in the production of thyroid-specific cargo proteins and ER-Golgi transport factors, and a parallel expansion of the Golgi complex. TSH also increased expression of the CREB3L1 transcription factor, which alone caused amplified transport factor levels and Golgi enlargement. Furthermore, CREB3L1 potentiated the TSH-induced increase in Golgi volume. A dominant-negative CREB3L1 construct hampered the ability of TSH to induce Golgi expansion, implying that this transcription factor contributes to Golgi expansion. Our findings support a model in which CREB3L1 acts as a downstream effector of TSH to regulate the expression of cargo proteins, and simultaneously increases the synthesis of transport factors and the expansion of the Golgi to synchronize the rise in cargo load with the amplified capacity of the secretory pathway.

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