LAMTOR2/LAMTOR1 complex is required for TAX1BP1‐mediated xenophagy. (21st January 2019)

• Record Type: Journal Article
• Authors: Lin, Ching‐Yu; Nozawa, Takashi; Minowa‐Nozawa, Atsuko; Toh, Hirotaka; Aikawa, Chihiro; Nakagawa, Ichiro
• Is Part Of: Cellular microbiology. Volume 21:Number 4(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-01-21
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12981
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: Xenophagy, also known as antibacterial autophagy, plays a role in host defence against invading pathogens such as Group A Streptococcus (GAS) and Salmonella . In xenophagy, autophagy receptors are used in the recognition of invading pathogens and in autophagosome maturation and autolysosome formation. However, the mechanism by which autophagy receptors are regulated during bacterial infection remains poorly elucidated. In this study, we identified LAMTOR2 and LAMTOR1, also named p14 and p18, respectively, as previously unrecognised xenophagy regulators that modulate the autophagy receptor TAX1BP1 in response to GAS and Salmonella invasion. LAMTOR1 was localized to bacterium‐containing endosomes, and LAMTOR2 was recruited to bacterium‐containing damaged endosomes in a LAMTOR1‐dependent manner. LAMTOR2 was dispensable for the formation of autophagosomes targeting damaged membrane debris surrounding cytosolic bacteria, but it was critical for autolysosome formation, and LAMTOR2 interacted with the autophagy receptors NBR1, TAX1BP1, and p62 and was necessary for TAX1BP1 recruitment to pathogen‐containing autophagosomes. Notably, knockout of TAX1BP1 caused a reduction in autolysosome formation and subsequent bacterial degradation. Collectively, our findings demonstrated that the LAMTOR1/2 complex is required for recruiting TAX1BP1 to autophagosomes and thereby facilitating autolysosome formation during bacterial infection. Abstract : Xenophagy uses autophagy receptors, such as TAX1BP1, in the recognition of invading pathogens, in autophagosome maturation, and in autolysosome formation. However, the mechanism by which autophagy receptors are regulated during bacterial infection remains poorly elucidated. This study demonstrated that LAMTOR2 and LAMTOR1 are previously unrecognized xenophagy regulators that modulate the autophagy receptor TAX1BP1 in response to GAS and Salmonella invasion.