The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling

Mol Cell. 2014 Apr 24;54(2):289-96. doi: 10.1016/j.molcel.2014.03.040.

Abstract

The innate immune system deploys a variety of sensors to detect signs of infection. Nucleic acids represent a major class of pathogen signatures that can trigger robust immune responses. The presence of DNA in the cytoplasm of mammalian cells is a danger signal that activates innate immune responses; however, how cytosolic DNA triggers these responses remained unclear until recently. In this review, we focus on the mechanism of DNA sensing by the newly discovered cGAS-cGAMP-STING pathway and highlight recent progress in dissecting the in vivo functions of this pathway in immune defense as well as autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Cytosol / metabolism*
  • DNA / metabolism*
  • Humans
  • Immunity, Innate / genetics*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Models, Immunological*
  • Models, Molecular
  • Nucleotides, Cyclic / metabolism
  • Nucleotides, Cyclic / physiology*
  • Nucleotidyltransferases / metabolism
  • Nucleotidyltransferases / physiology*
  • Signal Transduction

Substances

  • Membrane Proteins
  • Nucleotides, Cyclic
  • cyclic guanosine monophosphate-adenosine monophosphate
  • DNA
  • Nucleotidyltransferases