Endosomal trafficking of two-pore K⁺ efflux channel TWIK2 to plasmalemma mediates NLRP3 inflammasome activation and inflammatory injury.

ABSTRACT: Potassium efflux via the two-pore K⁺ channel TWIK2 is a requisite step for the activation of NLRP3 inflammasome, however, it remains unclear how K⁺ efflux is activated in response to select cues. Here, we report that during homeostasis, TWIK2 resides in endosomal compartments. TWIK2 is transported by endosomal fusion to the plasmalemma in response to increased extracellular ATP resulting in the extrusion of K⁺. We showed that ATP-induced endosomal TWIK2 plasmalemma translocation is regulated by Rab11a. Deleting Rab11a or ATP-ligated purinergic receptor P2X7 each prevented endosomal fusion with the plasmalemma and K⁺ efflux as well as NLRP3 inflammasome activation in macrophages. Adoptive transfer of Rab11a-depleted macrophages into mouse lungs pr

SUBMITTER: Huang LS 

PROVIDER: S-EPMC10202452 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature