Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8

• Published in: Scientific reports 2017-10, Vol.7 (1), p.13278-13, Article 13278
• Main Authors: Kim, Hyun-Taek, Lee, Mi-Sun, Jeong, Yun-Mi, Ro, Hyunju, Kim, Dong-Il, Shin, Yong-Hwan, Kim, Ji-Eun, Hwang, Kyu-Seok, Choi, Jung-Hwa, Bahn, Minjin, Lee, Jeong-Ju, Lee, Sang H., Bae, Young-Ki, Lee, Jin-Soo, Choi, Joong-Kook, Kim, Nam-Soon, Yeo, Chang-Yeol, Kim, Cheol-Hee
• Format: Article
• Language: English
• Subjects: 13/1; 14/63; 38; 38/32; 631/136; 631/136/1660; 64; 64/116; 82; Animals; Antisense DNA; Cell Membrane - metabolism; Cell surface; Cloning; Danio rerio; DNA, Complementary - genetics; Embryonic Development - genetics; Embryos; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Gene Expression; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genes; Genotype & phenotype; Glycosylation; Homeostasis; Humanities and Social Sciences; Humans; Membrane trafficking; Morphology; multidisciplinary; Pattern formation; Phenotype; Protein Binding; Protein Transport; Proteins; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Transcriptome; Wnt protein; Wnt Signaling Pathway; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13429-6

Wnt signaling controls critical developmental processes including tissue/body patterning. Here we report the identification of a novel regulator of Wnt signaling, OTTOGI (OTG) , isolated from a large-scale expression screening of human cDNAs in zebrafish embryos. Overexpression of OTG in zebrafish embryos caused dorso-anteriorized phenotype, inhibited the expression of Wnt target genes, and prevented nuclear accumulation of β-catenin. Conversely, knockdown of zebrafish otg using specific antisense morpholino promoted nuclear accumulation of β-catenin and caused ventralization. However, OTG failed to rescue headless -like phenotype induced by inhibition of GSK-3β activity, suggesting that OTG acts upstream of GSK-3β. OTG bound specifically to Frizzled8 (Fz8) receptor and caused retention of Fz8 in the endoplasmic reticulum possibly by preventing N-linked glycosylation of Fz8. Taken together, our data indicate that OTG functions as a novel negative regulator of Wnt signaling during development by the modulation of cell surface expression of Fz receptor.