RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial Autophagy

Robert J Heath1, Gautam Goel1, Leigh A Baxt1

  • 1Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Cell Reports
|November 24, 2016
PubMed

Insights

Researchers identified RNF166 as a key E3 ubiquitin ligase in antibacterial autophagy. This finding expands the understanding of how cells eliminate pathogens via selective autophagy.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Xenophagy is selective autophagy crucial for eliminating intracellular pathogens.
  • E3 ubiquitin ligases are vital for substrate selectivity in ubiquitination but their role in antibacterial autophagy is not fully mapped.

Purpose of the Study:

  • To systematically screen human E3 ligases for their roles in antibacterial autophagy.
  • To identify key regulators of adaptor protein and ubiquitin recruitment to bacteria during xenophagy.

Main Methods:

  • Screened over 600 putative human E3 ligases.
  • Utilized unbiased informatics to identify key genes.
  • Performed mechanistic studies to elucidate ubiquitination events.

Main Results:

  • Identified E3 ligases essential for adaptor protein recruitment and LC3-bacteria colocalization.
  • Pinpointed RNF166 as a critical E3 ligase regulating ubiquitin and adaptor protein (p62, NDP52) recruitment to bacteria.
  • Demonstrated RNF166 catalyzes K29- and K33-linked polyubiquitination of p62.

Conclusions:

  • Expands the known repertoire of E3 ligases involved in antibacterial autophagy.
  • Establishes a critical role for RNF166 in mediating xenophagy through specific p62 polyubiquitination.

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