Rabaptin5 targets autophagy to damaged endosomes and Salmonella vacuoles via FIP200 and ATG16L1

Selective autophagy of damaged organelles is important to maintain 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 identify two novel Rabapt...

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Bibliographic Details
Published in:EMBO reports 2022-01, Vol.23 (1), p.e53429-n/a
Main Authors: Millarte, Valentina, Schlienger, Simon, Kälin, Simone, Spiess, Martin
Format: Article
Language:English
Subjects:
ATG16L1
Autophagy
Autophagy-Related Proteins - genetics
Autophagy-Related Proteins - metabolism
Chloroquine
early endosomes
EMBO07
EMBO20
EMBO23
Endosomes
Endosomes - metabolism
Homeostasis
Infections
Monensin
Organelles
Phagosomes
Phagosomes - metabolism
Quality control
Rabaptin5
Salmonella
Salmonella enterica
Salmonella‐containing vacuoles
Vacuoles
Vacuoles - metabolism
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
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Summary:Selective autophagy of damaged organelles is important to maintain 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 identify 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. Autophagy of early endosomes damaged by chloroquine or monensin treatment requires Rabaptin5 and particularly a short sequence motif that binds to the WD domain of ATG16L1. Rabaptin5 and its interaction with ATG16L1 further contributes to the autophagic elimination of Salmonella enterica early after infection, when it resides in phagosomes with early endosomal characteristics. Our results demonstrate a novel function of Rabaptin5 in quality control of early endosomes in the selective targeting of autophagy to damaged early endosomes and phagosomes. Synopsis The endosomal regulator Rabaptin5 selectively targets autophagy to endosomes damaged by chloroquine or Salmonella infection via interaction with FIP200 and ATG16L1. Rabaptin5 binds FIP200 and ATG16L1 and selectively targets autophagy to early endosomes damaged by chloroquine treatment or Salmonella infection. A mutant form of Rabaptin5 deficient in ATG16L1‐binding prevents autophagosome formation upon chloroquine treatment. Rabaptin5 contributes to autophagic elimination of Salmonella enterica in early phagosomes. Graphical Abstract The endosomal regulator Rabaptin5 selectively targets autophagy to endosomes damaged by chloroquine or Salmonella infection via interaction with FIP200 and ATG16L1.
ISSN:1469-221X
1469-3178
DOI:10.15252/embr.202153429