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J Cell Sci. 2017 Jul 15;130(14):2251-2265. doi: 10.1242/jcs.199521. Epub 2017 May 23.

TRAPPC13 modulates autophagy and the response to Golgi stress.

Author information

1
Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.
2
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
3
Merck Serono TA Oncology, Merck KGaA, Frankfurter Str. 250, Darmstadt D-64293, Germany.
4
Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany reiling@bio.mx.

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.

KEYWORDS:

Autophagy; Brefeldin A; Golgi apparatus; Shigella flexneri; TRAPP complex

PMID:
28536105
PMCID:
PMC6518214
DOI:
10.1242/jcs.199521
[Indexed for MEDLINE]
Free PMC Article

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