|ZFIN ID: ZDB-PUB-120227-12|
|Source:||Journal of Cell Science 125(9): 2224-2234 (Journal)|
|Registered Authors:||Takada, Shinji|
|Keywords:||wnt, secretion, lipidation, porcupine, convergent extension, zebrafish|
|PubMed:||22357957 Full text @ J. Cell Sci.|
Porcupine (Porcn), an O-acyltransferase located in the endoplasmic reticulum (ER), is required for lipidation of Wnt proteins in mammalian culture cells, and Porcn-mediated lipidation is required for trafficking of Wnt proteins from the ER. However, it is still unclear whether Porcn is equivalently required for trafficking of all members of the Wnt family. In this study, we investigated the function of Porcn in zebrafish embryos. We identified two zebrafish homologs of porcupine, porcn and porcupine-like (porcn-l). Zebrafish porcn, but not porcn-l, restores secretion of Wnt proteins in porcn-deficient mouse L cells. Morpholino-mediated knockdown of porcn in zebrafish embryos impairs convergence and extension (CE) during gastrulation without changing embryonic patterning. Moreover, porcn interacts genetically with wnt5b and wnt11 in regulating CE. In contrast, porcn-deficient embryos do not exhibit phenotypes caused by failure in canonical Wnt signaling, which is activated by several Wnt ligands, including Wnt3a. Furthermore, expression of genes regulated by the canonical Wnt signaling pathway is not perturbed in knockdown embryos relative to that in the controls. While the trafficking and lipidation of ectopically expressed zebrafish Wnt5b and mouse Wnt5a are impaired in porcn-deficient embryos, those of ectopically expressed Wnt3a are less or no affected. In addition, the secretion of Wnt5a is inhibited by less amount of Porcn inhibitor than that of Wnt3a in HEK293T cells. Thus, decrease of Porcn activity does not equivalently affect trafficking and lipidation of different Wnt proteins in zebrafish embryos and in mammalian culture cells.
Original title: Deficiency of Porcupine, an O-acyltransferase gene, impairs convergent extension during gastrulation in zebrafish embryos and does not affect equivalently the trafficking of different Wnt proteins