The TRA PPI II complex activates the GTPase Ypt1 (Rab1) in the secretory pathway

Rab GTPases serve as molecular switches to regulate eukaryotic membrane trafficking pathways. The transport protein particle (TRA PP) complexes activate Rab GTPases by catalyzing GDP/GTP nucleotide exchange. In mammalian cells, there are two distinct TRA PP complexes, yet in budding yeast, four distinct TRA PP complexes have been reported. The apparent differences between the compositions of yeast and mammalian TRA PP complexes have prevented a clear understanding of the specific functions of TRA PP complexes in all cell types. In this study, we demonstrate that akin to mammalian cells, wild-type yeast possess only two TRA PP complexes, TRA PPII and TRA PPI II. We find that TRA PPI II plays a major role in regulating Rab activation and trafficking at the Golgi in addition to its established role in autophagy. These disparate pathways share a common regulatory GTPase Ypt1 (Rab1) that is activated by TRA PPI II. Our findings lead to a simple yet comprehensive model for TRA PPI II function in both normal and starved eukaryotic cells.