RETRACTED: Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins (Retracted Article)

被引:646
作者
Martinez, Jennifer [1 ]
Malireddi, R. K. Subbarao [1 ]
Lu, Qun [2 ]
Cunha, Larissa Dias [1 ]
Pelletier, Stephane [1 ,3 ]
Gingras, Sebastien [1 ,3 ]
Orchard, Robert [2 ]
Guan, Jun-Lin [4 ]
Tan, Haiyan [5 ]
Peng, Junmin [5 ,6 ,7 ]
Kanneganti, Thirumala-Devi [1 ]
Virgin, Herbert W. [2 ]
Green, Douglas R. [1 ]
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
[3] St Jude Childrens Res Hosp, Embryon Stem Cell Lab, Memphis, TN 38105 USA
[4] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45267 USA
[5] St Jude Childrens Res Hosp, St Jude Prote Facil, Memphis, TN 38105 USA
[6] St Jude Childrens Res Hosp, Dept Biol Struct, Memphis, TN 38105 USA
[7] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA
基金
美国国家卫生研究院;
关键词
NADPH OXIDASE ACTIVATION; GENOME-WIDE ASSOCIATION; NONCANONICAL AUTOPHAGY; REGULATE AUTOPHAGY; CROHN-DISEASE; CELL-DEATH; MICE; INFLAMMATION; GENERATION; MATURATION;
D O I
10.1038/ncb3192
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:893 / 906
页数:14
相关论文
共 54 条
[1]   The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology [J].
Bedard, Karen ;
Krause, Karl-Heinz .
PHYSIOLOGICAL REVIEWS, 2007, 87 (01) :245-313
[2]   Generation and Biological Activities of Oxidized Phospholipids [J].
Bochkov, Valery N. ;
Oskolkova, Olga V. ;
Birukov, Konstantin G. ;
Levonen, Anna-Liisa ;
Binder, Christoph J. ;
Stoeckl, Johannes .
ANTIOXIDANTS & REDOX SIGNALING, 2010, 12 (08) :1009-1059
[3]   Role of Autophagy and Autophagy Genes in Inflammatory Bowel Disease [J].
Cadwell, Ken ;
Stappenbeck, Thaddeus S. ;
Virgin, Herbert W. .
AUTOPHAGY IN INFECTION AND IMMUNITY, 2009, 335 :141-167
[4]   The Parasitophorous Vacuole Membrane of Toxoplasma gondii Is Targeted for Disruption by Ubiquitin-like Conjugation Systems of Autophagy [J].
Choi, Jayoung ;
Park, Sunmin ;
Biering, Scott B. ;
Selleck, Elizabeth ;
Liu, Catherine Y. ;
Zhang, Xin ;
Fujita, Naonobu ;
Saitoh, Tatsuya ;
Akira, Shizuo ;
Yoshimori, Tamotsu ;
Sibley, L. David ;
Hwang, Seungmin ;
Virgin, Herbert W. .
IMMUNITY, 2014, 40 (06) :924-935
[5]   The Legionella Effector RavZ Inhibits Host Autophagy Through Irreversible Atg8 Deconjugation [J].
Choy, Augustine ;
Dancourt, Julia ;
Mugo, Brian ;
O'Connor, Tamara J. ;
Isberg, Ralph R. ;
Melia, Thomas J. ;
Roy, Craig R. .
SCIENCE, 2012, 338 (6110) :1072-1076
[6]   IL-1 receptor blockade restores autophagy and reduces inflammation in chronic granulomatous disease in mice and in humans [J].
de Luca, Antonella ;
Smeekens, Sanne P. ;
Casagrande, Andrea ;
Iannitti, Rossana ;
Conway, Kara L. ;
Gresnigt, Mark. S. ;
Begun, Jakob ;
Plantinga, Theo S. ;
Joosten, Leo A. B. ;
van der Meer, Jos W. M. ;
Chamilos, Georgios ;
Netea, Mihai G. ;
Xavier, Ramnik J. ;
Dinarello, Charles A. ;
Romani, Luigina ;
van de Veerdonk, Frank L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (09) :3526-3531
[7]   Regulation of NADPH Oxidase Activity in Phagocytes RELATIONSHIP BETWEEN FAD/NADPH BINDING AND OXIDASE COMPLEX ASSEMBLY [J].
Debeurme, Franck ;
Picciocchi, Antoine ;
Dagher, Marie-Claire ;
Grunwald, Didier ;
Beaumel, Sylvain ;
Fieschi, Franck ;
Stasia, Marie-Jose .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (43) :33197-33208
[8]   Ambra1 regulates autophagy and development of the nervous system [J].
Fimia, Gian Maria ;
Stoykova, Anastassia ;
Romagnoli, Alessandra ;
Giunta, Luigi ;
Di Bartolomeo, Sabrina ;
Nardacci, Roberta ;
Corazzari, Marco ;
Fuoco, Claudia ;
Ucar, Ahmet ;
Schwartz, Peter ;
Gruss, Peter ;
Piacentini, Mauro ;
Chowdhury, Kamal ;
Cecconi, Francesco .
NATURE, 2007, 447 (7148) :1121-U14
[9]   Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes [J].
Florey, Oliver ;
Kim, Sung Eun ;
Sandoval, Cynthia P. ;
Haynes, Cole M. ;
Overholtzer, Michael .
NATURE CELL BIOLOGY, 2011, 13 (11) :1335-U118
[10]   Mitochondria and the Autophagy-Inflammation-Cell Death Axis in Organismal Aging [J].
Green, Douglas R. ;
Galluzzi, Lorenzo ;
Kroemer, Guido .
SCIENCE, 2011, 333 (6046) :1109-1112