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Title: Delivery of Cytosolic Components by Autophagic Adaptor Protein p62 Endows Autophagosomes with Unique Antimicrobial Properties
Authors: Marisa Ponpuak
Alexander S. Davis
Esteban A. Roberts
Monica A. Delgado
Christina Dinkins
Zijiang Zhao
Herbert W. Virgin
George B. Kyei
Terje Johansen
Isabelle Vergne
Vojo Deretic
University of New Mexico School of Medicine
Mahidol University
Washington University School of Medicine in St. Louis
UiT The Arctic University of Norway
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Mar-2010
Citation: Immunity. Vol.32, No.3 (2010), 329-341
Abstract: Autophagy allows cells to self-digest portions of their own cytoplasm for a multitude of physiological purposes, including innate and adaptive immunity functions. In one of its innate immunity manifestations, autophagy, is known to contribute to the killing of intracellular microbes, including Mycobacterium tuberculosis, although the molecular mechanisms have been unclear. Here, we delineated sequential steps of the autophagic pathway necessary to control intracellular M. tuberculosis and found that in addition to autophagy initiation and maturation, an accessory autophagy-targeting molecule p62 (A170 or SQSTM1) was required for mycobactericidal activity. The p62 adaptor protein delivered specific ribosomal and bulk ubiquitinated cytosolic proteins to autolysosomes where they were proteolytically converted into products capable of killing M. tuberculosis. Thus, p62 brings cytosolic proteins to autolysosomes where they are processed from innocuous precursors into neo-antimicrobial peptides, explaining in part the unique bactericidal properties of autophagic organelles. © 2010 Elsevier Inc.
ISSN: 10747613
Appears in Collections:Scopus 2006-2010

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