Figure 1.

(A) A model for assembly and activation of inflammasomes at the centrosome. NLRP3 protein is largely associated with the ER before stimulation and becomes associated with mitochondrion or trans-Golgi network (TGN) where it is engages ASC to form complex that is trafficked to the centrosome along the microtubules (MTs) by the HDAC6-Dynein motor machinery. At the centrosome NLRP3 and ASC interact with NEK7 and Caspase1 to finish assembly and activation. The Pyrin inflammasome is similarly assembled and activated at the centrosome. It’s likely that the AIM2 inflammasome might also be activated at the centrosome via an unknown mechanism. (B) Regulation of NLRP3 inflammasome at the centrosome by the centrosomal deubiquitinase complex Spata2-CYLD. Spata2-CYLD mediates the deubiquitination of PLK4 to promote PLK4 phosphorylation of NEK7, which inhibits NEK7-NLRP3 interaction and thereby NLRP3 inflammasome activation. (C) NLRP3 inflammasome assembled at the centrosome can exit into autophagosomes that fuse with lysosomes to cause inflammasome degradation.