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.

译文

:许多细胞的专业化,包括唾液腺和胰腺的腺泡细胞,乳腺产生乳汁的细胞,粘液分泌的杯状细胞,产生抗体的浆细胞以及产生密集的骨和软骨细胞外基质的细胞,需要扩大分泌机器和特定于细胞类型的分泌货物的规模。使用组织特异性基因组规模的分析,我们确定果蝇唾液腺(SG)中分泌能力的增加如何与分泌负荷的增加协调起来,果蝇唾液腺(SG)是获得有关分泌器官功能专业化的机制的理想模型。我们的发现表明,bZIP转录因子CrebA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货物转运子,Cop I和Cop II囊泡以及结构蛋白和酶。这些细胞器。 CrebA直接结合SG货物基因的一个子集,而CrebA结合并增强Sage的表达,Sage是货物表达必不可少的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总体分泌能力。直接和间接实现了货运量的同时增加。

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