Adenomatosis polyposis down-regulated 1(APCDD1) is a transmembrane glycoprotein that negatively regulates Wnt/β-catenin canonical signaling by binding with Wnt ligands and receptors. We analyzed the role of APCDD1 in...Adenomatosis polyposis down-regulated 1(APCDD1) is a transmembrane glycoprotein that negatively regulates Wnt/β-catenin canonical signaling by binding with Wnt ligands and receptors. We analyzed the role of APCDD1 in the Wnt5a/c-Jun non-canonical signaling pathway and demonstrated that APCDD1 can interact in vitro with Wnt5a, a classical ligand, and Ror2, a receptor of non-canonical Wnt signaling. Furthermore, we verified the binding of APCDD1 and Ror2 in primary cells of mouse skin. Moreover, APCDD1 seems to form a complex with Ror2 and Vangl2 in the cell, and complex formation can be improved by adding Wnt5a. In the presence of Wnt5a and Ror2, APCDD1 can induce the phosphorylation of c-Jun, a transcription factor of Wnt5a non-canonical signaling, and its phosphorylation level is a readout of Wnt5 a signaling. Wound-healing assay shows that APCDD1 accelerates polarized cell migration during Wnt5a-induced wound closure. Therefore,it is very likely that APCDD1 regulates Wnt5a/c-Jun non-canonical signaling as co-receptor binding with both Wnt5a and Ror2.展开更多
基金the National Natural Science Foundation of China(Nos.31671504 and 81421061)the Cross Research Fund of Biomedical Engineering of Shanghai Jiao Tong University(No.YG2016MS04)+1 种基金the Natural Science Foundation of Shanghai(No.13ZR1421100)the National Key Technology R&D Program of China(No.2012BAI01B09)
文摘Adenomatosis polyposis down-regulated 1(APCDD1) is a transmembrane glycoprotein that negatively regulates Wnt/β-catenin canonical signaling by binding with Wnt ligands and receptors. We analyzed the role of APCDD1 in the Wnt5a/c-Jun non-canonical signaling pathway and demonstrated that APCDD1 can interact in vitro with Wnt5a, a classical ligand, and Ror2, a receptor of non-canonical Wnt signaling. Furthermore, we verified the binding of APCDD1 and Ror2 in primary cells of mouse skin. Moreover, APCDD1 seems to form a complex with Ror2 and Vangl2 in the cell, and complex formation can be improved by adding Wnt5a. In the presence of Wnt5a and Ror2, APCDD1 can induce the phosphorylation of c-Jun, a transcription factor of Wnt5a non-canonical signaling, and its phosphorylation level is a readout of Wnt5 a signaling. Wound-healing assay shows that APCDD1 accelerates polarized cell migration during Wnt5a-induced wound closure. Therefore,it is very likely that APCDD1 regulates Wnt5a/c-Jun non-canonical signaling as co-receptor binding with both Wnt5a and Ror2.
