Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin
Open Access
- 7 October 2013
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 203 (1), 115-128
- https://doi.org/10.1083/jcb.201304188
Abstract
Although ubiquitin is thought to be important for the autophagic sequestration of invading bacteria (also called xenophagy), its precise role remains largely enigmatic. Here we determined how ubiquitin is involved in this process. After invasion, ubiquitin is conjugated to host cellular proteins in endosomes that contain Salmonella or transfection reagent–coated latex (polystyrene) beads, which mimic invading bacteria. Ubiquitin is recognized by the autophagic machinery independently of the LC3–ubiquitin interaction through adaptor proteins, including a direct interaction between ubiquitin and Atg16L1. To ensure that invading pathogens are captured and degraded, Atg16L1 targeting is secured by two backup systems that anchor Atg16L1 to ubiquitin-decorated endosomes. Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3.Keywords
This publication has 45 references indexed in Scilit:
- Ubiquitination-mediated autophagy against invading bacteriaCurrent Opinion in Cell Biology, 2011
- Differential Involvement of Atg16L1 in Crohn Disease and Canonical AutophagyJournal of Biological Chemistry, 2009
- Shigella Phagocytic Vacuolar Membrane Remnants Participate in the Cellular Response to Pathogen Invasion and Are Regulated by AutophagyCell Host & Microbe, 2009
- Role of ULK-FIP200 complex in mammalian autophagy: FIP200, a counterpart of yeast Atg17?Autophagy, 2009
- An Atg4B Mutant Hampers the Lipidation of LC3 Paralogues and Causes Defects in Autophagosome ClosureMolecular Biology of the Cell, 2008
- The Atg16L Complex Specifies the Site of LC3 Lipidation for Membrane Biogenesis in AutophagyMolecular Biology of the Cell, 2008
- Autophagy recognizes intracellular Salmonella enterica serovar Typhimurium in damaged vacuoles.Autophagy, 2006
- High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cellsNucleic Acids Research, 2002
- Noncanonical MMS2-Encoded Ubiquitin-Conjugating Enzyme Functions in Assembly of Novel Polyubiquitin Chains for DNA RepairCell, 1999
- Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatusThe Journal of cell biology, 1994