| First Author | Shen C | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 23 | Pages | 5759-5774.e20 |
| PubMed ID | 34678144 | Mgi Jnum | J:316943 |
| Mgi Id | MGI:6833928 | Doi | 10.1016/j.cell.2021.09.032 |
| Citation | Shen C, et al. (2021) Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome. Cell 184(23):5759-5774.e20 |
| abstractText | NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here, we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with double-stranded RNA (dsRNA) in vitro and in cells, and an intrinsically disordered poly-lysine sequence (K350-354) of NLRP6 is important for multivalent interactions, phase separation, and inflammasome activation. Nlrp6-deficient or Nlrp6(K350-354A) mutant mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, implicating NLRP6 LLPS in anti-microbial immunity. Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. Lipoteichoic acid, a known NLRP6 ligand, also promotes NLRP6 LLPS, and DHX15, a helicase in NLRP6-induced interferon signaling, co-forms condensates with NLRP6 and dsRNA. Thus, LLPS of NLRP6 is a common response to ligand stimulation, which serves to direct NLRP6 to distinct functional outcomes depending on the cellular context. |
