Rabaptin5 targets autophagy to damaged early endosomes and Salmonella containing vacuoles by interaction with FIP200 and ATG16L1

Abstract

Selective autophagy of damaged organelles is an important process for cellular homeostasis. The mechanisms how autophagy selects specific targets is often poorly understood. Rabaptin5 was previously known as a major regulator of early endosome identity and maturation. Here we identified two novel Rabaptin5 interactors: FIP200, a subunit of the ULK1 autophagy initiator complex, and ATG16L1, a central component of the E3-like enzyme in LC3 lipidation. Indeed, autophagy of early endosomes damaged by chloroquine or monensin treatment was found to require Rabaptin5 and particularly a specific short sequence motif binding to the WD domain of ATG16L1. Rabaptin5 and this interaction with ATG16L1 is further required for much of autophagic elimination of Salmonella enterica in phagosomes with early endosomal characteristics early after infection. Our results demonstrate a novel function of Rabaptin5 in quality control of early endosomes in the selective recruitment of autophagy to damaged early endosomes and phagosomes.