A CREB3-ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens.
| Title: | A CREB3-ARF4 signalling pathway mediates the response to Golgi stress and susceptibility to pathogens. |
|---|---|
| Authors: | Reiling JH; 1] 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].; Olive AJ; Sanyal S; Carette JE; Brummelkamp TR; Ploegh HL; Starnbach MN; Sabatini DM |
| Source: | Nature cell biology [Nat Cell Biol] 2013 Dec; Vol. 15 (12), pp. 1473-85. Date of Electronic Publication: 2013 Nov 03. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Macmillan Magazines Ltd Country of Publication: England NLM ID: 100890575 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4679 (Electronic) Linking ISSN: 14657392 NLM ISO Abbreviation: Nat Cell Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London : Macmillan Magazines Ltd., [1999- |
| MeSH Terms: | Stress, Physiological*; ADP-Ribosylation Factors/*metabolism ; Cyclic AMP Response Element-Binding Protein/*metabolism ; Golgi Apparatus/*physiology; ADP-Ribosylation Factor 1/genetics ; ADP-Ribosylation Factor 1/metabolism ; ADP-Ribosylation Factors/genetics ; Brefeldin A/pharmacology ; Chlamydia trachomatis/physiology ; Golgi Apparatus/drug effects ; Guanine Nucleotide Exchange Factors/genetics ; Guanine Nucleotide Exchange Factors/metabolism ; Protein Transport/drug effects ; RNA, Small Interfering/genetics ; Shigella flexneri/physiology ; Disease Susceptibility ; Gene Knockdown Techniques ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Signal Transduction ; Transcriptional Activation ; Up-Regulation |
| 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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| Grant Information: | R01 CA103866 United States CA NCI NIH HHS; R01 CA129105 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute; CA103866 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (CREB3 protein, human); 0 (Cyclic AMP Response Element-Binding Protein); 0 (GBF1 protein, human); 0 (Guanine Nucleotide Exchange Factors); 0 (RNA, Small Interfering); 20350-15-6 (Brefeldin A); EC 3.6.5.2 (ADP-Ribosylation Factor 1); EC 3.6.5.2 (ADP-Ribosylation Factors); EC 3.6.5.2 (ARF4 protein, human) |
| Entry Date(s): | Date Created: 20131105 Date Completed: 20140204 Latest Revision: 20211021 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3965854 |
| DOI: | 10.1038/ncb2865 |
| PMID: | 24185178 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't