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

Dorothy M. Johnson, Michael B. Wells, Rebecca Fox, Joslynn S Lee, Rajprasad Loganathan, Daniel C Levings, Abigail Bastien, Matthew Slattery, Deborah J. Andrew

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)560-577
Number of pages18
JournalTraffic
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2020

Bibliographical note

Funding Information:
We thank M. Papadakis, J. Guzman and T. Zou for sequencing help. We thank P. O'Farrell for the EnP1 antiserum used in the SG secretion assays. We thank M. Luchetti for assistance with polytene chromosome immunostaining. We thank members of the Andrew Lab for helpful discussions and we thank S. Michaelis, J. Pomeranz, B. Cormack and C. Machamer for advice at different stages of this project. This project was only possible because of the fly data curation provided by Flybase. This work was supported by NIH RO1 DE013899 to DJA, NIH K99 DE021461 to RMF, and NIH F31 DE023721 to DMJ. 58

Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • ChIP-seq
  • CrebA
  • Drosophila
  • TSN
  • Xbp1
  • sage
  • salivary gland
  • secretory capacity
  • secretory cargo
  • transcription factor

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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