Novel and conventional inhibitors of canonical autophagy differently affect LC3-associated phagocytosis

FEBS Letters

article

Femmy C. Stempels¹  Maaike H. Janssens¹  Martin ter Beest²  Rob J. Mesman³  Natalia H. Revelo²  Melina Ioannidis¹  Geert van den Bogaart¹ 

[1] Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen;Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center;Department of Microbiology, RIBES, Faculty of Science, Radboud University Nijmegen

关键词: autophagy;    bafilomycin A1;    chloroquine;    EACC;    LAP;    LC3-associated phagocytosis;    SAR405;   

DOI  :  10.1002/1873-3468.14280

来源: John Wiley & Sons Ltd.

【 摘 要 】

In autophagy, LC3-positive autophagophores fuse and encapsulate the autophagic cargo in a double-membrane structure. In contrast, lipidated LC3 (LC3-II) is directly formed at the phagosomal membrane in LC3-associated phagocytosis (LAP). In this study, we dissected the effects of autophagy inhibitors on LAP. SAR405, an inhibitor of VPS34, reduced levels of LC3-II and inhibited LAP. In contrast, the inhibitors of endosomal acidification bafilomycin A1 and chloroquine increased levels of LC3-II, due to reduced degradation in acidic lysosomes. However, while bafilomycin A1 inhibited LAP, chloroquine did not. Finally, EACC, which inhibits the fusion of autophagosomes with lysosomes, promoted LC3 degradation possibly by the proteasome. Targeting LAP with small molecule inhibitors is important given its emerging role in infectious and autoimmune diseases.

【 授权许可】

Unknown