ZFIN ID: ZDB-PUB-030117-3
Caspy: A Zebrafish caspase activated by ASC oligomerization required for pharyngeal arch development
Masumoto, J., Zhou, W., Chen, F.F., Su, F., Kuwada, J.Y., Hidaka, E., Katsuyama, T., Sagara, J., Taniguchi, S., Ngo-Hazelett, P., Postlethwait, J.H., Nuñez, G., and Inohara, N.
Date: 2003
Source: The Journal of biological chemistry 278(6): 4268-4276 (Journal)
Registered Authors: Inohara, Naohiro, Kuwada, John, Ngo-Hazelett, Phuong, Postlethwait, John H., Su, Fengyun, Zhou, Weibin
Keywords: none
MeSH Terms: Amino Acid Sequence; Animals; Apoptosis; Base Sequence; Biopolymers (all 21) expand
PubMed: 12464617 Full text @ J. Biol. Chem.
FIGURES   (current status)
ABSTRACT
The pyrin domain was recently identified in multiple proteins which 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 which was 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 CARD-containing protein previously identified 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 gene 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 which plays an important role in the morphogenesis of the jaw and gill-bearing arches.
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