Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2013 Dec;15(12):1473-85. doi: 10.1038/ncb2865. Epub 2013 Nov 3.

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

Author information

  • 11] Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts Institute of Technology (MIT), Department of Biology, Cambridge, Massachusetts 02142, USA [3] Koch Institute for Integrative Cancer Research, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [4].


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.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk