Abstract
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 Wnt5a 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.
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Foundation item: 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), the Natural Science Foundation of Shanghai (No. 13ZR1421100), and the National Key Technology R&D Program of China (No. 2012BAI01B09)
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Wang, L., Tao, Y., Zhang, J. et al. APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway. J. Shanghai Jiaotong Univ. (Sci.) 24, 510–516 (2019). https://doi.org/10.1007/s12204-019-2083-5
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DOI: https://doi.org/10.1007/s12204-019-2083-5