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The autophagy regulator Rubicon is a feedback inhibitor of CARD9-mediated host innate immunity

Chul-Su Yang1, Mary Rodgers, Chan-Ki Min

  • 1Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA.

Cell Host & Microbe
|March 20, 2012
PubMed

Insights

Rubicon protein inhibits CARD9, BCL10, and MALT1 (CBM) complex signaling, acting as a feedback mechanism for pattern recognition receptors (PRRs). This prevents excessive inflammation and regulates immune responses to infection.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • The CARD9, BCL10, and MALT1 (CBM) complex is essential for pattern recognition receptor (PRR) signaling, including Dectin and RIG-I.
  • Rubicon protein regulates autophagy and phagocytosis, interacting with Beclin-UVRAG-Vps34 and NADPH oxidase complexes.

Purpose of the Study:

  • To investigate Rubicon's role in CBM-mediated PRR signaling.
  • To determine if Rubicon acts as a feedback inhibitor of PRR signaling pathways.

Main Methods:

  • Studied Rubicon's interactions with the CBM complex upon Dectin-1 or RIG-I activation.
  • Investigated Rubicon's phosphorylation-dependent binding partner exchange.
  • Assessed the functional and genetic separability of Rubicon's roles in different cellular complexes.

Main Results:

  • Rubicon dynamically binds to CARD9, disassembling the CBM complex and inhibiting PRR signaling.
  • This interaction is stimulation-specific and phosphorylation-dependent, terminating cytokine production.
  • Rubicon's functions in autophagy, phagocytosis, and CBM complexes are functionally and genetically distinct.

Conclusions:

  • Rubicon acts as a physiological feedback inhibitor of CBM-mediated PRR signaling.
  • Rubicon prevents overactive inflammatory responses by regulating CBM complex assembly.
  • Rubicon differentially targets signaling complexes to coordinate immune responses against microbial threats.

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