| First Author | Dick MS | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11929 | PubMed ID | 27329339 |
| Mgi Jnum | J:240072 | Mgi Id | MGI:5882288 |
| Doi | 10.1038/ncomms11929 | Citation | Dick MS, et al. (2016) ASC filament formation serves as a signal amplification mechanism for inflammasomes. Nat Commun 7:11929 |
| abstractText | A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). Here we show that assembly of the ASC speck involves oligomerization of ASC(PYD) into filaments and cross-linking of these filaments by ASC(CARD). ASC mutants with a non-functional CARD only assemble filaments but not specks, and moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis of ASC(PYD) is used to identify oligomerization-deficient ASC mutants and demonstrate that ASC speck formation is required for efficient processing of IL-1beta, but dispensable for gasdermin-D cleavage and pyroptosis induction. Our results suggest that the oligomerization of ASC creates a multitude of potential caspase-1 activation sites, thus serving as a signal amplification mechanism for inflammasome-mediated cytokine production. |
