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Cited by 169Cellular transport and secretionEndoplasmic Reticulum Stress and DiseaseAutophagy in Disease and Therapy

A CREB3–ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens

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Reiling, Jan H., Olive, Andrew J., Sanyal, Sumana, Carette, Jan E., Brummelkamp, Thijn R., Ploegh, Hidde L., Starnbach, Michael N., Sabatini, David M.·2013·Nature Cell Biology
DOI 10.1038/ncb2865PMC PMC3965854
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Abstract

Treatment of cells with brefeldin A (BFA) blocks secretory vesicle transport and causes a collapse of the Golgi apparatus. To gain more insight into the cellular mechanisms mediating BFA toxicity, we conducted a genome-wide haploid genetic screen that led to the identification of the small G protein ADP-ribosylation factor 4 (ARF4). ARF4 depletion preserves viability, Golgi integrity and cargo trafficking in the presence of BFA, and these effects depend on the guanine nucleotide exchange factor GBF1 and other ARF isoforms including ARF1 and ARF5. ARF4 knockdown cells show increased resistance to several human pathogens including Chlamydia trachomatis and Shigella flexneri. Furthermore, ARF4 expression is induced when cells are exposed to several Golgi-disturbing agents and requires the CREB3 (also known as Luman or LZIP) transcription factor, whose downregulation mimics ARF4 loss. Thus, we have uncovered a CREB3-ARF4 signalling cascade that may be part of a Golgi stress response set in motion by stimuli compromising Golgi capacity.

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Authors
Reiling, J. H., Olive, A. J., Sanyal, S., Carette, J. E., Brummelkamp, T. R., Ploegh, H. L., Starnbach, M. N., & Sabatini, D. M.
Affiliations
  • Whitehead Institute for Biomedical Research (US)
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
  • Reiling, Jan H.
  • Sabatini, David M.
ORCID
Venue
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2013-11-03
Volume
15
Issue
12
Pages
1473-1485
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
DOI
10.1038/ncb2865
PMC
PMC3965854
OpenAlex
W2048165620
Cited by
169
References
3
Citations by year
2026: 13 · 2025: 12 · 2024: 16 · 2023: 14 · 2022: 16 · 2021: 9 · 2020: 5 · 2019: 17 · 2018: 12 · 2017: 18 · 2016: 9 · 2015: 16 · 2014: 10
FWCI
5.38
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • PMC
Funders
  • Howard Hughes Medical Institute
  • Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
  • National Institutes of Health
  • National Cancer Institute (CA103866, R01CA103866, R01CA129105)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
Golgi stress, ARF4, CREB3, brefeldin A, secretory vesicle transport, Golgi apparatus, GBF1, Chlamydia trachomatis, Shigella flexneri, insertional mutagenesis, cell death
MeSH terms
Chlamydia trachomatis, Disease Susceptibility, Golgi Apparatus, HeLa Cells, Humans, Shigella flexneri, Stress, Physiological, Signal Transduction, Transcriptional Activation, Up-Regulation, Cyclic AMP Response Element-Binding Protein, Brefeldin A, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factors, ADP-Ribosylation Factor 1, Protein Transport, RNA, Small Interfering, Host-Pathogen Interactions, Gene Knockdown Techniques

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