Convergence of secretory, endosomal, and autophagic routes in trans-Golgi-associated lysosomes

Zhou et al. document that the vicinity of the trans-Golgi is the main location for lysosomes in Drosophila cells. They also show that the trans-Golgi-associated degradative compartment, where basal microautophagy of secretory cargos normally takes place, additionally contributes to autophagic vesicle formation under stress conditions. At the trans-Golgi, complex traffic connections exist to the endolysosomal system additional to the main Golgi-to-plasma membrane secretory route. Here, we investigated three hits in a Drosophila screen displaying secretory cargo accumulation in autophagic vesicles: ESCRT-III component Vps20, SNARE-binding Rop, and lysosomal pump subunit VhaPPA1-1. We found that Vps20, Rop, and lysosomal markers localize near the trans-Golgi. Furthermore, we document that the vicinity of the trans-Golgi is the main cellular location for lysosomes and that early, late, and recycling endosomes associate as well with a trans-Golgi-associated degradative compartment where basal microautophagy of secretory cargo and other materials occurs. Disruption of this compartment causes cargo accumulation in our hits, including Munc18 homolog Rop, required with Syx1 and Syx4 for Rab11-mediated endosomal recycling. Finally, besides basal microautophagy, we show that the trans-Golgi-associated degradative compartment contributes to the growth of autophagic vesicles in developmental and starvation-induced macroautophagy. Our results argue that the fly trans-Golgi is the gravitational center of the whole endomembrane system.

Automated summary

The study reveals that the trans-Golgi is the main location for lysosomes in Drosophila cells, where basal microautophagy of secretory cargos normally takes place, and contributes to autophagic vesicle formation under stress conditions.