APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

doi:10.1007/s12204-019-2083-5

Journal of Shanghai Jiao Tong University (Science) ›› 2019, Vol. 24 ›› Issue (4): 510-516.doi: 10.1007/s12204-019-2083-5

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APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

WANG Lei (王磊), TAO Yixin (陶一昕), ZHANG Jie (张洁), WANG Xiaoqing (王晓晴), ZHOU Shanghui (周晌辉), HE Lin (贺林), MA Gang *(马钢)

(1. Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; 2. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China; 3. Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 4. Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China)
(1. Bio-X-Renji Hospital Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China; 2. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China; 3. Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 4. Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China)

Online:2019-08-01 Published:2019-07-29
Contact: MA Gang *(马钢) E-mail:magang@sjtu.edu.cn

Abstract

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.

Key words: adenomatosis polyposis down-regulated 1 (APCDD1)| Wnt signaling| receptor| Wnt5a| polarized cell migration

摘要： 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.

关键词: adenomatosis polyposis down-regulated 1 (APCDD1)| Wnt signaling| receptor| Wnt5a| polarized cell migration

CLC Number:

Q 753

WANG Lei (王磊), TAO Yixin (陶一昕), ZHANG Jie (张洁), WANG Xiaoqing (王晓晴), ZHOU Shanghui (周晌辉), HE Lin (贺林), MA Gang *(马钢). APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway[J]. Journal of Shanghai Jiao Tong University (Science), 2019, 24(4): 510-516.

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APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

APCDD1 as a Co-receptor Positively Regulates Wnt5a/c-Jun Non-Canonical Signaling Pathway

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