Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8
- Kim, H.T., Lee, M.S., Jeong, Y.M., Ro, H., Kim, D.I., Shin, Y.H., Kim, J.E., Hwang, K.S., Choi, J.H., Bahn, M., Lee, J.J., Lee, S.H., Bae, Y.K., Lee, J.S., Choi, J.K., Kim, N.S., Yeo, C.Y., Kim, C.H.
- Scientific Reports 7: 13278 (Journal)
- Registered Authors
- Bae, Young Ki, Choi, Jung-Hwa, Kim, Cheol-Hee, Kim, Dong-Il, Kim, Hyun-Taek, Lee, Mi-Sun
- MeSH Terms
- Cell Membrane/metabolism*
- DNA, Complementary/genetics
- Embryonic Development/genetics
- Endoplasmic Reticulum/metabolism
- Gene Expression
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- Protein Binding
- Protein Transport
- Receptors, Cell Surface/metabolism*
- Wnt Signaling Pathway*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- 29038508 Full text @ Sci. Rep.
Kim, H.T., Lee, M.S., Jeong, Y.M., Ro, H., Kim, D.I., Shin, Y.H., Kim, J.E., Hwang, K.S., Choi, J.H., Bahn, M., Lee, J.J., Lee, S.H., Bae, Y.K., Lee, J.S., Choi, J.K., Kim, N.S., Yeo, C.Y., Kim, C.H. (2017) Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8. Scientific Reports. 7:13278.
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.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes