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2016 ; 213
(5
): 771-90
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English Wikipedia
A single domain antibody fragment that recognizes the adaptor ASC defines the
role of ASC domains in inflammasome assembly
#MMPMID27069117
Schmidt FI
; Lu A
; Chen JW
; Ruan J
; Tang C
; Wu H
; Ploegh HL
J Exp Med
2016[May]; 213
(5
): 771-90
PMID27069117
show ga
Myeloid cells assemble inflammasomes in response to infection or cell damage;
cytosolic sensors activate pro-caspase-1, indirectly for the most part, via the
adaptors ASC and NLRC4. This leads to secretion of proinflammatory cytokines and
pyroptosis. To explore complex formation under physiological conditions, we
generated an alpaca single domain antibody, VHHASC, which specifically recognizes
the CARD of human ASC via its type II interface. VHHASC not only impairs
ASC(CARD) interactions in vitro, but also inhibits inflammasome activation in
response to NLRP3, AIM2, and NAIP triggers when expressed in living cells,
highlighting a role of ASC in all three types of inflammasomes. VHHASC leaves the
Pyrin domain of ASC functional and stabilizes a filamentous intermediate of
inflammasome activation. Incorporation of VHHASC-EGFP into these structures
allowed the visualization of endogenous ASC(PYD) filaments for the first time.
These data revealed that cross-linking of ASC(PYD) filaments via ASC(CARD)
mediates the assembly of ASC foci.