Duplication of the caspase-12 prodomain and inactivation of NLRC4/IPAF in the dog.
Caspases-1, 4, 5, and 12 and other proteins containing caspase recruitment domains (CARDs) play crucial roles in the induction of inflammatory processes. Recently, hybrid caspase-1/4 mRNAs encoding proteases with two CARDs were identified in cat and dog, indicating that the molecular machinery of caspase-dependent inflammation has an unconventional composition in members of the order Carnivora. Here we extended these studies and identified, both in cat and dog, splice variants of caspase-12, which also contained two CARDs. Comparative genomics analysis of the repertoire of canine CARD proteins revealed that the gene encoding NLRC4/IPAF, which is implicated in the inflammatory response to cytosolic flagellin, was inactivated by deleterious mutations in the dog. Our results demonstrate that the repertoires of CARD proteins in cat and dog differ significantly from that of humans and suggest the existence of uncharacterized pathways of inflammasome-mediated signaling in Carnivora.
Eckhart
Leopold
L
Department of Dermatology, Medical University of Vienna, A-1090 Vienna, Austria. leopold.eckhart@meduniwien.ac.at
Ballaun
Claudia
C
Uthman
Aumaid
A
Gawlas
Sonja
S
Buchberger
Maria
M
Fischer
Heinz
H
Tschachler
Erwin
E
D000595:Amino Acid Sequence; D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D053454:Caspase 12 / Q000235:genetics*; D002415:Cats; D004285:Dogs / Q000235:genetics*; D020440:Gene Duplication; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion
D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D053454:Caspase 12