The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family

The Drosophila segment polarity gene product Porcupine (Porc) was first ide ntified as being necessary for processing Wingless (Wg), a Drosophila Wnt ( Wnt) family member. Mouse and Xenopus homologs of porc (Mporc and Xporc) we re identified and found to encode endoplasmic reticulum (ER) proteins with multiple transmembrane domains. In contrast with porc, four different types of Mporc and Xporc mRNA (A-D) are generated from a single gene by alternat ive splicing. Mporc mRNA is differentially expressed during embryogenesis a nd in various adult tissues, demonstrating that the alternative splicing is regulated to synthesize the specific types of Mporc. In transfected mammal ian cells, all Mporc types affect the processing of mouse Wnt 1, 3A, 4, 6, and 7B but not 5A. Furthermore, all Mporc types are co-immunoprecipitated w ith various Wnt proteins. These results suggest that Mporc may function as a chaperone-like molecule for Wnt. Interestingly, all Mporc types can subst itute for Porc, as they are able to rescue the phenotypes of Drosophila por c embryos. Consistent with this observation, Mporc, like Porc, modifies the processing of Wg expressed in mammalian cells. These results demonstrate t hat the porc gene family encodes the multitransmembrane ER proteins, which are evolutionarily well conserved and involved in processing the Wnt family .