CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells
CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells
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DOI：
10.1242/jcs.211102
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Alvarez, Cecilia
中科院分区：
文献类型：
--
作者：
Garcia, Iris A.;Torres Demichelis, Vanina;Alvarez, Cecilia
许多分泌细胞响应于特定刺激而增加货物蛋白的合成和分泌。细胞如何将增加的货物负荷与分泌能力的协调上升结合起来以确保有效的运输尚不清楚。我们使用促甲状腺激素（TSH）刺激的甲状腺细胞，以证明甲状腺特异性货物蛋白和ER-高尔基体转运因子的产生协调增加，以及高尔基体复合体的平行扩增。促甲状腺激素也增加CREB 3L 1转录因子的表达，这单独导致放大的运输因子水平和高尔基体扩大。此外，CREB 3L 1增强TSH诱导的高尔基体体积的增加。显性负CREB 3L 1结构阻碍了TSH诱导高尔基体扩张的能力，这意味着这种转录因子有助于高尔基体扩张。我们的研究结果支持一种模型，其中CREB 3L 1作为TSH的下游效应子来调节货物蛋白的表达，同时增加运输因子的合成和高尔基体的扩张，以同步货物负荷的增加与分泌途径的放大能力。
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.