CARD-Bcl10-Malt1 signalosomes: missing link to NF-kappaB.

CARD11 (CARMA1), Bcl10, and Malt1 are required for nuclear factor NF-kappaB activation in response to antigen recognition. Initially, gene disruption experiments in mice pointed to a lymphocyte-specific role for CARD11-Bcl10-Malt1 complexes. However, strong evidence suggesting that conserved Bcl10-Malt1 complexes interact with different CARD scaffolds to connect various receptors in different cell types to NF-kappaB signaling has emerged more recently. The CARD10 (CARMA3)-Bcl10-Malt1 signalosome functions as a link between G protein-coupled receptor (GPCR) signaling and proinflammatory NF-kappaB activation. Further, Dectin-1-induced antifungal responses to NF-kappaB in dendritic cells depend on CARD9-Bcl10-Malt1. These results identify CARD-Bcl10-Malt1 signalosomes as pivotal regulators that link not only innate and adaptive immune responses, but also GPCR signaling, to the canonical NF-kappaB pathway.