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

Abstract

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.

Copper‐independent lysosomal localisation of the Wilson disease protein ATP7B

“…To circumvent copper‐induced toxicity, this type of direct transport ensures faster response in elevated copper conditions. A recent study has shown that TGN‐associated lysosome acts as a hub for secretory, endosomal, and autophagic routes in drosophila 52 . Interestingly, we found that an increase in TGN46‐LAMP2 colocalisation is positively correlated with copper‐induced endolysosomal localisation of ATP7B that increases with increasing copper (Figure 5A,B).…”

“…A recent study has shown that TGN-associated lysosome acts as a hub for secretory, endosomal, and autophagic routes in drosophila. 52 Interestingly, we found that an increase in TGN46-LAMP2 colocalisation is positively correlated with copper-induced endolysosomal localisation of ATP7B that increases with increasing copper (Figure 5A,B). We further explored if these TGN-proximal lysosomes serve as a 'distribution hub' for endolysosomal dispersal (trafficking) of ATP7B in elevated copper.…”

Copper-independent lysosomal localization of the Wilson disease protein ATP7B

“…To circumvent copper-induced toxicity, this type of direct transport ensures faster response in elevated copper condition. A recent study has shown that TGN associated lysosome acts as a hub for secretory, endosomal and autophagic route in drosophila (Zhou et al, 2023). Interestingly, we found that increase in TGN46-LAMP2 colocalisation is positively correlated with copper-induced endolysosomal localisation of ATP7B that increases with increasing copper (fig 5A, 5B).…”

G1P3/IFI6, an interferon stimulated protein, promotes the association of RAB5+ endosomes with mitochondria in breast cancer cells

“…The early or sorting endosomes are thought to be maintained by the continuous transport of vesicles from the plasma membrane and TGN (Grant & Donaldson, 2009). However, recent studies suggest that vesicles emerging from TGN and not from plasma membrane are indispensable for the formation of RAB5 + endosomes (Nagano et al, 2019; Zhou et al, 2023). Additionally, RAB5 is suggested to regulate the process of endo‐lysosomal trafficking from TGN (Grant & Donaldson, 2009; Nagano et al, 2019; Woodman, 2000; Zhou et al, 2023).…”

“…However, recent studies suggest that vesicles emerging from TGN and not from plasma membrane are indispensable for the formation of RAB5 + endosomes (Nagano et al, 2019; Zhou et al, 2023). Additionally, RAB5 is suggested to regulate the process of endo‐lysosomal trafficking from TGN (Grant & Donaldson, 2009; Nagano et al, 2019; Woodman, 2000; Zhou et al, 2023). The colocalization of G1P3 with RAB5, TGN, and lysosomal markers suggests the trafficking of G1P3 from TGN into endolysosomes (Figure 5).…”