HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation

TLDR

Inflammasome complexes form in response to pathogen‑associated molecules, initiating cytokine maturation and pyroptosis, and are characterized by a single supramolecular speck per cell, though the location and mechanism of speck formation remain poorly understood. The study shows that NLRP3 and pyrin inflammasomes assemble and function at the MTOC, a process that depends on the dynein adaptor HDAC6 and links aggresome formation and autophagic degradation to efficient inflammasome regulation. Magupalli et al., Science, this issue p.

Abstract

The MTOC is “speck”-tacular Inflammasome complexes are formed in response to pathogen-associated molecules. They initiate both the maturation of inflammatory cytokines and pyroptosis, a type of programmed cell death. One notable feature for inflammasome activation is the formation of a single supramolecular punctum (or “speck”) in each affected cell. However, the location and mechanism of speck formation is poorly understood. Magupalli et al. report that for NLRP3- and pyrin-mediated inflammasomes, their assembly and downstream functions occur at the microtubule-organizing center (MTOC). This process requires the dynein adaptor HDAC6, which is also a central player in aggresome formation and autophagosomal degradation at the MTOC. This work links several important cellular processes and provides clues for how inflammasomes are efficiently regulated. Science , this issue p. eaas8995