CrebA increases secretory capacity through direct transcriptional regulation of the secretory machinery, a subset of secretory cargo, and other key regulators. (18th August 2020)

• Record Type: Journal Article
• Authors: Johnson, Dorothy M.; Wells, Michael B.; Fox, Rebecca; Lee, Joslynn S.; Loganathan, Rajprasad; Levings, Daniel; Bastien, Abigail; Slattery, Matthew; Andrew, Deborah J.
• Is Part Of: Traffic. Volume 21:Number 9(2020)
• Page Start: 560
• Page End: 577
• Publication Date: 2020-08-18
• Subjects: ChIP‐seq -- CrebA -- Drosophila -- sage -- salivary gland -- secretory capacity -- secretory cargo -- transcription factor -- TSN -- Xbp1; Biological transport -- Periodicals; 571.6
• DOI: 10.1111/tra.12753
• Languages: English
• ISSNs: 1398-9219

Abstract

Abstract: 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. Synopsis: CrebA, the Drosophila orthologue of the vertebrate Creb3/3L bZIP transcription factors, boosts cell secretory capacity. We show that the activation of genes encoding the core secretory machinery in the salivary glands occurs by direct CrebA binding and regulation. Direct binding of CrebA also boosts the expression of Sage, a transcription factor essential for cargo gene expression. To further enhance secretory output, CrebA binds and activates Xbp1— a key player in the unfolded protein response, and Tudor‐SN —an ER‐associated RNA‐binding protein.