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Atg5 regulates formation of MyD88 condensed structures and MyD88-dependent signal transduction

Megumi Inomata1, Takeshi Into, Shumpei Niida

  • 1Department of Oral Microbiology, Division of Oral Infections and Health Sciences, Asahi University School of Dentistry, Mizuho, Gifu, Japan. inomata@dent.asahi-u.ac.jp

Biochemical and Biophysical Research Communications
|July 9, 2013
PubMed

Insights

Autophagy protein Atg5 suppresses MyD88 condensed structures. Atg5 deficiency enhances MyD88-TRAF6 complex formation and NF-κB signaling activation, modulating Toll-like receptor signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Myeloid differentiation primary response 88 (MyD88) is a crucial adaptor protein for Toll-like receptors (TLRs).
  • While transfected MyD88 forms cytoplasmic structures, endogenous MyD88 condensed structures are suppressed upon TLR stimulation, with the underlying mechanism and significance remaining unclear.

Purpose of the Study:

  • To investigate the mechanism suppressing endogenous MyD88 condensed structure formation.
  • To elucidate the role of autophagy protein Atg5 in regulating MyD88 condensed structures and downstream signaling.

Main Methods:

  • Utilized Atg5-deficient cells to observe MyD88 structure formation.
  • Performed immunoprecipitation to assess Atg5-MyD88 interaction.
  • Analyzed MyD88-TRAF6 complex formation, NF-κB, MAPK, and Akt signaling activation following TLR stimulation.

Main Results:

  • Endogenous MyD88 condensed structures formed in Atg5-deficient cells and were further enhanced by TLR stimulation.
  • Atg5's suppressive effect on MyD88 structures was independent of canonical autophagy.
  • Atg5 interacts with MyD88, and Atg5 deficiency potentiated MyD88-TRAF6 complex formation and NF-κB activation.

Conclusions:

  • Atg5 directly inhibits the formation of MyD88 condensed structures through association with MyD88.
  • Atg5 modulates MyD88-dependent signaling pathways, specifically impacting NF-κB activation.
  • These findings reveal a novel regulatory role for Atg5 in innate immune signaling.
Keywords:
AutophagyCondensed structuresMyD88Signal transductionToll-like receptors (TLRs)

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