TRAPPC13 modulates autophagy and the response to Golgi stress

Abstract

Tether complexes play important roles in endo- and exocytic trafficking of lipids and proteins. In yeast, the multisubunit transport protein particle (TRAPP) tether regulates ER-Golgi, intra-Golgi transport and is also implicated in autophagy. The TRAPP complex in addition acts as a GEF for Ypt1, which is homologous to human Rab1. 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, which is dependent on ARF1 and the large GEF GBF1 and concomitant with reduced caspase activation and ER stress marker induction. TRAPPC13 depletion furthermore reduces Rab1 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.