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TRIM-directed selective autophagy regulates immune activation.

Authors
  • 1
  • 2
  • 1
  • 1
  • 2
  • 1
  • 1 a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Albuquerque , NM , USA.
  • 2 b Molecular Cancer Research Group , Institute of Medical Biology, University of Tromsø-The Arctic University of Norway , Tromsø , Norway.
Type
Published Article
Journal
Autophagy
1554-8635
Publisher
Landes Bioscience
Publication Date
Volume
13
Issue
5
Pages
989–990
Identifiers
DOI: 10.1080/15548627.2016.1154254
PMID: 26983397
Source
Medline
Keywords
License
Unknown

Abstract

Selectivity of autophagy is achieved by target recognition; however, the number of autophagy receptors identified so far is limited. In this study we demonstrate that a subset of tripartite motif (TRIM) proteins mediate selective autophagy of key regulators of inflammatory signaling. MEFV/TRIM20, and TRIM21 act as autophagic receptors recognizing their cognate targets and delivering them for autophagic degradation. MEFV recognizes the inflammasome components NLRP3, CASP1 and NLRP1, whereas TRIM21 specifically recognizes the activated, dimeric from of IRF3 inducing type I interferon gene expression. MEFV and TRIM21 have a second activity, whereby they act not only as receptors but also recruit and organize key components of autophagic machinery consisting of ULK1, BECN1, ATG16L1, and mammalian homologs of Atg8, with a preference for GABARAP. MEFV capacity to organize the autophagy apparatus is affected by common mutations causing familial Mediterranean fever. These findings reveal a general mode of action of TRIMs as autophagic receptor-regulators performing a highly-selective type of autophagy (precision autophagy), with MEFV specializing in the suppression of inflammasome and CASP1 activation engendering IL1B/interleukin-1β production and implicated in the form of cell death termed pyroptosis, whereas TRIM21 dampens type I interferon responses.

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