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Nature Studies Identify Lipid 'Dimmer' That Tunes STING Activity

The phosphoinositide PI(3,5)P2 directly binds the immune sensor, reframing activation as more than a cGAMP switch.

Overview

  • Two independent papers report that STING responds to the membrane lipid PI(3,5)P2 in addition to the nucleotide messenger cGAMP.
  • Cryo-electron microscopy from a separate lab confirms that PI(3,5)P2 binds STING.
  • Cells unable to produce PI(3,5)P2 show suppressed STING signaling, demonstrating a functional role for the lipid.
  • Researchers describe cGAMP as an on–off trigger and PI(3,5)P2 as a dimmer that modulates the strength of the inflammatory response.
  • Experts note that PIKfyve is the sole kinase that generates PI(3,5)P2, and altering its activity also affects other phosphoinositides and cellular processes.