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Nat Cell Biol. 2015 Jul;17(7):893-906. doi: 10.1038/ncb3192. Epub 2015 Jun 22.

Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins.

Author information

1
Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
2
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA.
3
1] Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2] Embryonic Stem Cell Laboratory, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
4
Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
5
St Jude Proteomics Facility, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
6
1] St Jude Proteomics Facility, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA [2] Departments of Structural Biology and Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Abstract

LC3-associated phagocytosis (LAP) is a process wherein elements of autophagy conjugate LC3 to phagosomal membranes. We characterize the molecular requirements for LAP, and identify Rubicon as being required for LAP but not autophagy. Rubicon is recruited to LAPosomes and is required for the activity of a Class III PI(3)K complex containing UVRAG but lacking ATG14 and Ambra1. This allows for the sustained localization of PtdIns(3)P, which is critical for recruitment of downstream autophagic proteins and stabilization of the NOX2 complex to produce reactive oxygen species. Both PtdIns(3)P and reactive oxygen species are required for conjugation of LC3 to LAPosomes and subsequent association with LAMP1(+) lysosomes. LAP is induced by engulfment of Aspergillus fumigatus, a fungal pathogen that commonly afflicts immunocompromised hosts, and is required for its optimal clearance in vivo. Therefore, we have identified molecules that distinguish LAP from canonical autophagy, thereby elucidating the importance of LAP in response to A. fumigatus infection.

Comment in

PMID:
26098576
PMCID:
PMC4612372
DOI:
10.1038/ncb3192
[Indexed for MEDLINE]
Free PMC Article

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