The Atg17-Atg31-Atg29 Complex Coordinates with Atg11 to Recruit the Vam7 SNARE and Mediate Autophagosome-Vacuole Fusion

Macroautophagy (hereafter autophagy) is an evolutionarily conserved process in which portions of the cytoplasm are engulfed, degraded, and subsequently recycled. The Atg17-Atg31-Atg29 complex translocates to the phagophore assembly site (PAS), where an autophagosome forms, at a very early stage of autophagy, playing a vital role in autophagy induction. Here, we identified a novel role of this complex in a late stage of autophagy where it coordinates with Atg11 to regulate autophagy-specific fusion with the vacuole. Atg17 and Atg11 interact with the vacuolar SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) Vam7 independently of each other. Several hydrophobic residues in helix 1 and helix 4 of Atg17 and the SNARE domain of Vam7 mediate the Atg17-Vam7 interaction. An F317D mutation of Atg17, which diminishes its interaction with Vam7 without affecting its interaction with Atg13 or Atg31, leads to a defect in the fusion of autophagosomes with the vacuole and decreased autophagy activity. These results provide the first demonstration that the Atg17-Atg31-Atg29 complex functions in both early and late stages of autophagy and also provide a mechanistic explanation for the coordination of autophagosome completion and fusion with the vacuole. [Display omitted] •The Atg17-Atg31-Atg29 complex and Atg11 recruit Vam7 to the PAS during autophagy•Atg17 directly interacts with the SNARE domain of Vam7•Hydrophobic residues L105, F317, and I325 of Atg17 mediate its binding to Vam7•Recruitment of Vam7 to the PAS is required for autophagosome-vacuole fusion Liu et al. show that the Atg17-Atg31-Atg29 complex not only plays an essential role in autophagy induction but also regulates autophagosome-vacuole fusion. Specifically diminishing recruitment of the vacuolar SNARE Vam7 to the phagophore assembly site by the ternary complex and Atg11 results in defects in autophagosome-vacuole fusion.