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In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...
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Molecular and spatial mechanisms governing STING signalling.

Katherine R Balka1, Dominic De Nardo1

  • 1Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Vic., Australia.

The FEBS Journal
|November 25, 2020
PubMed
Summary

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is crucial for host defense against pathogens. This review details STING

Keywords:
IKKεNF-κBSTINGTBK1cGAScytokinesinnate immunityprotein traffickingsignal transductiontype I IFNs

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Innate immunity relies on detecting microbial nucleic acids through specific receptors.
  • The cGAS-STING pathway is a critical DNA-sensing mechanism for antiviral and antibacterial defense.
  • STING activation leads to type I interferon (IFN) secretion via IRF3 and pro-inflammatory cytokines via NF-κB.

Purpose of the Study:

  • To review the current understanding of STING-mediated inflammatory and antimicrobial responses.
  • To focus on the signaling mechanisms and intracellular trafficking of STING.
  • To discuss emerging concepts, including IFN-independent STING functions and STING-related diseases.

Main Methods:

  • Literature review of studies on cGAS-STING pathway signaling and regulation.
  • Analysis of research on STING trafficking and its impact on downstream pathways.
  • Synthesis of current knowledge on IRF3 and NF-κB activation downstream of STING.

Main Results:

  • STING signaling orchestrates both IFN-dependent and IFN-independent immune responses.
  • STING trafficking dynamics are critical for regulating the timing and extent of immune activation.
  • While the IRF3-IFN axis is well-studied, other STING-mediated responses require further elucidation.

Conclusions:

  • STING is a central regulator of innate immunity, with complex signaling and trafficking events.
  • Understanding STING's diverse roles, including IFN-independent functions, is vital for host defense.
  • Further research into STING signaling and its dysregulation in disease holds therapeutic potential.