Signaling through the inflammasome is important for the inflammatory response. Low concentrations of intracellular K⁺are associated with the specific oligomerization and activation of the NLRP3 inflammasome, a type of inflammasome involved in sterile inflammation. After NLRP3 oligomerization, ASC protein binds and forms oligomeric filaments that culminate in large protein complexes named ASC specks. ASC specks are also initiated from different inflammasome scaffolds, such as AIM2, NLRC4 or Pyrin. ASC oligomers recruit caspase-1 and then induce its activation through interactions between their respective caspase activation and recruitment domains (CARD). So far ASC oligomerization and caspase-1 activation are K⁺-independent processes. Here we found that, when there is low intracellular K⁺, ASC oligomers change their structure independently of NLRP3 and make the ASC^CARD domain more accessible for the recruitment of the pro-caspase-1^CARD domain. Therefore, conditions that decrease intracellular K⁺ not only drive NLRP3 responses but also enhance the recruitment of pro-caspase-1 CARD domain into the ASC specks.

Please see the README document and the accompanying published article: Fátima Martín-Sánchez, Vincent Compan, Alejandro Peñín-Franch, Ana Tapia-Abellán, Ana I. Gómez, María C. Baños-Gregori, Florian I. Schmidt, Pablo Pelegrín. ASC oligomer favors caspase-1CARD domain recruitment after intracellular potassium efflux. Journal of Cell Biology. 2023. https://doi.org/10.1083/jcb.202003053