TRAPPC13 modulates autophagy and the response to Golgi stress.
| Title: | TRAPPC13 modulates autophagy and the response to Golgi stress. |
|---|---|
| Authors: | Ramírez-Peinado S; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.; Ignashkova TI; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.; van Raam BJ; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.; Baumann J; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.; Sennott EL; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.; Gendarme M; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.; Lindemann RK; Merck Serono TA Oncology, Merck KGaA, Frankfurter Str. 250, Darmstadt D-64293, Germany.; Starnbach MN; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.; Reiling JH; Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany reiling@bio.mx. |
| Source: | Journal of cell science [J Cell Sci] 2017 Jul 15; Vol. 130 (14), pp. 2251-2265. Date of Electronic Publication: 2017 May 23. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Cambridge : Company of Biologists; Original Publication: London. |
| MeSH Terms: | Antigens, Neoplasm/*metabolism ; Golgi Apparatus/*metabolism ; Vesicular Transport Proteins/*metabolism; ADP-Ribosylation Factor 1/metabolism ; Anti-Bacterial Agents/pharmacology ; Antigens, Neoplasm/drug effects ; Autophagy/physiology ; Brefeldin A/pharmacology ; Dysentery, Bacillary/drug therapy ; Dysentery, Bacillary/metabolism ; Guanine Nucleotide Exchange Factors/metabolism ; Shigella flexneri/drug effects ; Vesicular Transport Proteins/antagonists & inhibitors ; Vesicular Transport Proteins/drug effects ; A549 Cells ; Gene Knockdown Techniques ; HEK293 Cells ; HT29 Cells ; HeLa Cells ; Humans |
| Abstract: | Tether complexes play important roles in endocytic and exocytic trafficking of lipids and proteins. In yeast, the multisubunit transport protein particle (TRAPP) tether regulates endoplasmic reticulum (ER)-to-Golgi and intra-Golgi transport and is also implicated in autophagy. In addition, the TRAPP complex acts as a guanine nucleotide exchange factor (GEF) for Ypt1, which is homologous to human Rab1a and Rab1b. Here, we show that human TRAPPC13 and other TRAPP subunits are critically involved in the survival response to several Golgi-disrupting agents. Loss of TRAPPC13 partially preserves the secretory pathway and viability in response to brefeldin A, in a manner that is dependent on ARF1 and the large GEF GBF1, and concomitant with reduced caspase activation and ER stress marker induction. TRAPPC13 depletion reduces Rab1a and Rab1b activity, impairs autophagy and leads to increased infectivity to the pathogenic bacterium Shigella flexneri in response to brefeldin A. Thus, our results lend support for the existence of a mammalian TRAPPIII complex containing TRAPPC13, which is important for autophagic flux under certain stress conditions.; (© 2017. Published by The Company of Biologists Ltd.) |
| Competing Interests: | Competing interestsThe authors declare no competing or financial interests. |
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| Grant Information: | R01 AI039558 United States AI NIAID NIH HHS; U19 AI113187 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: Autophagy; Brefeldin A; Golgi apparatus; Shigella flexneri; TRAPP complex |
| Substance Nomenclature: | 0 (Anti-Bacterial Agents); 0 (Antigens, Neoplasm); 0 (GBF1 protein, human); 0 (Guanine Nucleotide Exchange Factors); 0 (TRAPPC1 protein, human); 0 (Vesicular Transport Proteins); 20350-15-6 (Brefeldin A); EC 3.6.5.2 (ADP-Ribosylation Factor 1) |
| Entry Date(s): | Date Created: 20170525 Date Completed: 20180911 Latest Revision: 20220518 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC6518214 |
| DOI: | 10.1242/jcs.199521 |
| PMID: | 28536105 |
| Database: | MEDLINE |
Journal Article