PUBLICATION
Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8
- Authors
- 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.
- ID
- ZDB-PUB-171019-21
- Date
- 2017
- Source
- 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
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Membrane/metabolism*
- DNA, Complementary/genetics
- Embryonic Development/genetics
- Endoplasmic Reticulum/metabolism
- Gene Expression
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- Glycosylation
- Humans
- Phenotype
- Protein Binding
- Protein Transport
- Receptors, Cell Surface/metabolism*
- Transcriptome
- Wnt Signaling Pathway*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29038508 Full text @ Sci. Rep.
Citation
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.
Abstract
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping