The yeast multisubunit transport protein particle (TRAPP) is a tether that regulates transport from the ER to the Golgi, as well as within the Golgi, and has also been implicated in the regulation of autophagy. Furthermore, TRAPP also acts as a guanine nucleotide exchange factor (GEF) for Ypt1 (Rab1 in humans). In this study (p. 2251), Jan Reiling and colleagues investigate the effect of loss of the human TRAPP complex subunit TRAPPC13 (also known as C5orf44), which they had previously identified as rendering cells resistant to Brefeldin A (BFA)-mediated cell death. They show here that BFA treatment of TRAPPC13-depleted cells results in a more preserved secretory pathway, reduced apoptosis and induction of ER stress compared to what is seen in control cells. These effects are dependent on ARF1 and the GEF GBF1. Interestingly, loss of Rab1 mimics the effects of TRAPPC13 depletion, suggesting that TRAPPC13 is required for the GEF function of TRAPPC and that decreased levels of Rab1 are beneficial for cells to survive BFA-induced stress. In addition, the authors find that when these cells are treated with BFA, depletion of TRAPPC13 leads to a decrease in autophagic flux, as well as a higher survival rate of a bacterial pathogen. Further support for a direct role of TRAPPC13 in autophagy comes from its observed co-precipitation with the core autophagy factor Atg9. Taken together, these data demonstrate an important role for TRAPPC13 in regulating autophagy and cell survival under conditions of Golgi stress.
