The Role Of APCDD1 In Non-canonical Wnt Pathway

APCDD1(adenomatosis polyposis down-regulate 1)is a transmembrane glycoprotein,it can interact in vitro with Wnt canonical pathway ligand Wnt3 a and receptor LRP5.This kind of interaction can inhibit activation of downstream target genes and eventually suppressed various biological effects caused by the Wnt signaling pathway.As we all know that,in addition to the canonical Wnt signaling pathway,there is a non-canonical Wnt signaling pathway which is Wnt5 a ligand-based on,this pathway mainly affects cells and tissues motor ability and cell polarity.There are interaction and adjustment between canonical and noncanonical Wnt signaling pathway,for example,Frizzled participates in both of these two pathways as a receptor.Therefore,we speculated whether APCDD1 gene play any role in non-canonical Wnt signaling pathway?We first used immunoprecipitation to study the interaction between APCDD1 and non-canonical Wnt signaling pathway ligands and receptors,and found out that APCDD1 can combine both with Wnt5 a ligand and the important non-canonical signal receptor Ror2.Moreover,although APCDD1 can not bind with Vangl2 which is a co-receptor of non-canonical Wnt pathway solely,but in the presence of Ror2 receptor,we detected the binding of APCDD1 and Vangl2,while this kind of binding capacity can be further improved when simultaneously adding Wnt5 a ligands.Therefore,we hypothesized that APCDD1 act as a receptor to regulate the non-canonical Wnt signaling by mediating the formation of Ror2-Vangl2-APCDD1 complexs on the cell membrane.So,what was the actual impact of APCDD1 on this pathway,promote or inhibit it? Then,by detecting the phosphorylation of c-Jun which is an important transcription factor of non-canonical Wnt signaling,we found APCDD1 can increase the lever of phosphorylated c-jun,and this result implied APCDD1 promote non-canonical Wnt signaling pathway.Moreover,cell wound-healing assay also further confirmed this view: NIH3T3 cells which over expressed APCDD1 protein,can significantly improve the speed of cell migration and promote wound healing.Based on all the above results,we think APCDD1 protein participate in and regulate the canonical and non-canonical Wnt signaling pathway as a receptor.What is the difference is the effect of APCDD1 on canonical Wnt pathway is inhibitory,while for non-canonical Wnt signaling pathway is promotion.All of these new findings may provide an important basis to illustrate the mechanisms of APCDD1 gene in the Wnt non-canonical pathway.Next,we will detect whether APCDD1 protein also can combine with Wnt signaling receptor Ror2 in primary cells endogenously,explore the relationship between APCDD1 and Ror2 receptor,and whether APCDD1 involved in regulating the canonical and non-canonical Wnt signaling pathway.