title: Caspy, a zebrafish caspase, activated by ASC oligomerization is required for pharyngeal arch development.
abstract: The pyrin domain was identified recently in multiple proteins that are associated with apoptosis and/or inflammation, but the physiological and molecular function of these proteins remain poorly understood. We have identified Caspy and Caspy2, two zebrafish caspases containing N-terminal pyrin domains. Expression of Caspy and Caspy2 induced apoptosis in mammalian cells that were inhibited by general caspase inhibitors. Biochemical analysis revealed that both Caspy and Caspy2 are active caspases, but they exhibit different substrate specificity. Caspy, but not Caspy2, interacted with the zebrafish orthologue of ASC (zAsc), a pyrin- and caspase recruitment domain-containing protein identified previously in mammals. The pyrin domains of both Caspy and zAsc were required for their interaction. Furthermore, zAsc and Caspy co-localized to the "speck" when co-transfected into mammalian cells. Enforced oligomerization of zAsc, but not simple interaction with zAsc, induced specific proteolytic activation of Caspy and enhanced Caspy-dependent apoptosis. Injection of zebrafish embryos with a morpholino antisense oligonucleotide corresponding to caspy resulted in an "open mouth" phenotype associated with defective formation of the cartilaginous pharyngeal skeleton. These studies suggest that zAsc mediates the activation of Caspy, a caspase that plays an important role in the morphogenesis of the jaw and gill-bearing arches.
authors.affiliation: Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor 48109, USA. ino@umich.edu
authors.forename: Junya
authors.initials: J
authors.lastname: Masumoto
authors.forename: Weibin
authors.initials: W
authors.lastname: Zhou
authors.forename: Felicia F
authors.initials: FF
authors.lastname: Chen
authors.forename: Fengyun
authors.initials: F
authors.lastname: Su
authors.forename: John Y
authors.initials: JY
authors.lastname: Kuwada
authors.forename: Eiko
authors.initials: E
authors.lastname: Hidaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Katsuyama
authors.forename: Junji
authors.initials: J
authors.lastname: Sagara
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Phuong
authors.initials: P
authors.lastname: Ngo-Hazelett
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Naohiro
authors.initials: N
authors.lastname: Inohara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001704:Biopolymers; D020169:Caspases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers; D018076:DNA, Complementary; D004789:Enzyme Activation; D016678:Genome; D008969:Molecular Sequence Data; D010614:Pharynx / Q000196:embryology*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D029961:Zebrafish Proteins; C498533:pycard protein, zebrafish; D020169:Caspases; C472302:caspa protein, zebrafish