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. Author manuscript; available in PMC: 2022 Oct 21.
Published in final edited form as: Mol Cell. 2021 Oct 6;81(20):4137–4146. doi: 10.1016/j.molcel.2021.09.010

Figure 1. LLPS regulates cGAS signaling.

Figure 1.

(i) Cytosolic LLPS of cGAS is driven by several factors, including multivalent charge-charge interactions with dsDNA. These properties drive cGAS to undergo an abrupt phase transition to form condensates with dsDNA at a low threshold concentration. (ii) LLPS compartmentalizes the cGAS signaling machinery, forming a core cGAS/DNA condensate that is surrounded by a phase-separated outer shell containing TREX1, a dsDNA-degrading enzyme that antagonizes cGAS signaling. Depletion of dsDNA from the outer shell helps suppress TREX1 function and promote cGAS-mediated DNA sensing. The concentrated environment within the cGAS/DNA core dramatically enhances cGAS activity by increasing DNA-binding efficiency. (iii) cGAS self-associates via its core catalytic domain to form dimers along dsDNA strands, which activates cGAS to catalyze the conversion of GTP and ATP into cGAMP and induce additional downstream signaling.