NEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D.

ABSTRACT: The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K⁺ efflux. However, the mechanism by which K⁺ efflux promotes this interaction remains unknown. Here, we show that NEK7 is rapidly phosphorylated at threonine-190/191 by JNK1 downstream of K⁺ efflux and gasdermin D (GSDMD) after NLRP3 activation. NEK7 phosphorylation enhances the binding between NEK7 and NLRP3, which further promotes inflammasome assembly and activation. Mutant mice and macrophages in which Thr¹⁹⁰ and Thr¹⁹¹ of Nek7 were replaced by valine exhibited impaired NEK7 phosphorylation, NLRP3 inflammasome activation, and

SUBMITTER: Xu J 

PROVIDER: S-EPMC12020992 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature