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

By Jennifer Martinez, R. Malireddi, Q. Lu, L. D. Cunha, Stéphane Pelletier, S. Gingras, R. Orchard, J. Guan, Haiyan Tan, Junmin Peng and 3 more. Nature Cell Biology, 2015

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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.

Subfields: Epidemiology, Immunology, Physiology

View Paper: https://www.semanticscholar.org/paper/0071750e590b5bf51b5eb9244c518124fa49ddbf

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Citations in the corpus

Molecular definitions of autophagy and related processes (2017, positive): “…in the control of bacterial and fungal pathogens (Sanjuan et al , 2007; Zhao et al , 2008; Gong et al , 2011; Lam et al , 2013; Choi et al , 2014; Martinez et al , 2015; Selleck et al , 2015), in entosis (a variant of RCD that ensues engulfment by non-phagocytic cells) (Florey et al , 2011), as…”
Phagocytosis: An Immunobiologic Process. (2016, background): “Molecular characterization of LC3-associated phagocytosis has revealed distinct roles for the class III PI(3)K-associated protein Rubicon, NOX2 (NADPH oxidase 2), and autophagy proteins (Martinez et al., 2015).”
Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “A specific form of phagocytosis engaged by several pathogens and dead cell corpses, which is known as LC3-associated phagocytosis (LAP), depends on several proteins involved in bona fide autophagic responses (Martinez et al., 2015 (Martinez et al., , 2016 Sanjuan et al., 2007) .”
The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages (2019, background): “However, we cannot differentiate whether the effects of butyrate are linked to canonical autophagy or non-canonical LC3-associated phagocytosis pathways (Martinez et al., 2015).”