Zw10 negatively regulates the MyD88-mediated NF-κB signaling through autophagy in teleost fish

Baolan Cao1, Ya Chen1, Junxia Cui1

  • 1Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.

Insights

Zw10 protein targets MyD88 to inhibit NF-κB activation and innate immunity in fish. This study reveals Zw10 degrades MyD88 via autophagy, impacting teleost immune signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Myeloid differentiation primary response 88 (MyD88) is crucial for Toll-like receptor (TLR) signaling and innate immunity.
  • The NF-κB pathway activation by MyD88 promotes inflammatory factors.
  • Molecular mechanisms of MyD88-mediated NF-κB signaling in teleosts remain underexplored.

Purpose of the Study:

  • To investigate the role of Zw10 in regulating Myeloid differentiation primary response 88 (MyD88)-mediated NF-κB signaling in teleosts.
  • To elucidate the molecular mechanism by which Zw10 affects innate immunity.

Main Methods:

  • Investigated the interaction between Zw10 and MyD88.
  • Assessed the role of Zw10's Δ2 domain in MyD88 degradation.
  • Examined the involvement of autophagy in Zw10-mediated MyD88 regulation.

Main Results:

  • Zw10 targets and inhibits Myeloid differentiation primary response 88 (MyD88) activation of the NF-κB pathway.
  • Zw10 negatively regulates cell proliferation and MyD88-dependent innate immunity in fish.
  • Zw10 interacts with MyD88, with its Δ2 domain being critical for MyD88 degradation via autophagy.

Conclusions:

  • Zw10 acts as a negative regulator of the Myeloid differentiation primary response 88 (MyD88)-mediated NF-κB signaling pathway in teleosts.
  • Autophagy-dependent degradation of MyD88 by Zw10 is a key mechanism in innate immune regulation.
  • Findings contribute to understanding teleost innate immunity and offer insights into mammalian immune regulation.

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