CrebA increases secretory capacity through direct transcriptional regulation of the secretory machinery, a subset of secretory cargo, and other key regulators.,Traffic

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CrebA increases secretory capacity through direct transcriptional regulation of the secretory machinery, a subset of secretory cargo, and other key regulators.
Traffic ( IF 3.6 ) Pub Date : 2020-07-01 , DOI: 10.1111/tra.12753
Dorothy M Johnson ₁ , Michael B Wells ₁ , Rebecca Fox ₁ , Joslynn S Lee ₂ , Rajprasad Loganathan ₁ , Daniel Levings ₂ , Abigail Bastien ₁ , Matthew Slattery ₂ , Deborah J Andrew ₁

Affiliation

Specialization of many cells, including the acinar cells of the salivary glands and pancreas, milk‐producing cells of mammary glands, mucus‐secreting goblet cells, antibody‐producing plasma cells, and cells that generate the dense extracellular matrices of bone and cartilage, requires scaling up both secretory machinery and cell‐type specific secretory cargo. Using tissue‐specific genome‐scale analyses, we determine how increases in secretory capacity are coordinated with increases in secretory load in the Drosophila salivary gland (SG), an ideal model for gaining mechanistic insight into the functional specialization of secretory organs. Our findings show that CrebA, a bZIP transcription factor, directly binds genes encoding the core secretory machinery, including protein components of the signal recognition particle and receptor, ER cargo translocators, Cop I and Cop II vesicles, as well as the structural proteins and enzymes of these organelles. CrebA directly binds a subset of SG cargo genes and CrebA binds and boosts expression of Sage, a SG‐specific transcription factor essential for cargo expression. To further enhance secretory output, CrebA binds and activates Xbp1 and Tudor‐SN. Thus, CrebA directly upregulates the machinery of secretion and additional factors to increase overall secretory capacity in professional secretory cells; concomitant increases in cargo are achieved both directly and indirectly.

中文翻译：

CrebA 通过对分泌机制、分泌货物的一个子集和其他关键调节器的直接转录调节来增加分泌能力。

许多细胞的特化，包括唾液腺和胰腺的腺泡细胞、乳腺的产奶细胞、分泌粘液的杯状细胞、产生抗体的浆细胞，以及产生致密的骨和软骨细胞外基质的细胞，都需要扩大分泌机制和细胞类型特异性分泌物。使用组织特异性基因组规模分析，我们确定了分泌能力的增加如何与果蝇唾液腺 (SG) 分泌负荷的增加相协调，这是获得分泌器官功能专业化机制洞察的理想模型。我们的研究结果表明，CrebA 是一种 bZIP 转录因子，直接结合编码核心分泌机制的基因，包括信号识别颗粒和受体的蛋白质成分，ER 货物转运蛋白、Cop I 和 Cop II 囊泡，以及这些细胞器的结构蛋白和酶。CrebA 直接结合 SG 货物基因的一个子集，CrebA 结合并促进 Sage 的表达，Sage 是货物表达所必需的 SG 特异性转录因子。为了进一步增强分泌输出，CrebA 结合并激活Xbp1和Tudor-SN。因此，CrebA 直接上调分泌机制和其他因素，以增加专业分泌细胞的整体分泌能力；直接和间接地实现了货物的同步增长。

更新日期：2020-08-19

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