Distinct TRAPP complexes activate Ypt/Rab GTPases in secretion and autophagy

The conserved Ypt/Rab GTPases regulate all steps of the intracellular transport pathways. In yeast and human cells, Ypt1/Rab1 regulate early steps of secretion and autophagy, whereas Ypt31/Rab11 regulate a late step in secretion, and the TRAPP complexes act as their activators. The Ypt and transport step specificity of TRAPP complexes is currently controversial. Here, we use in vivo analyses of mutations in subunits of yeast TRAPP complexes to determine these specificities. First, deletion of the TRAPPIII-specific subunit Trs85 does not affect transport through the Golgi nor the localization of TRAPPI or Ypt1 to the Golgi. Second, conditional depletion of essential subunits of TRAPPI and TRAPPII shows that they are required for early and late secretion steps, respectively. Thus, TRAPPI and TRAPPII activate Ypt1 and Ypt31 in early- and late-Golgi, respectively, ascribing TRAPPIII in Ypt1 activation only in autophagy. This distinct activator assignment provides a mechanism for the dual function of Ypt1/Rab1 in secretion and autophagy, where Rab1 has been implicated in disease.