Ottogi inhibits Wnt/β-catenin signaling by regulating cell membrane trafficking of Frizzled8

Cited 2 time in scopus
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Title
Ottogi inhibits Wnt/β-catenin signaling by regulating cell membrane trafficking of Frizzled8
Author(s)
H T Kim; M S Lee; Y M Jeong; H Ro; D I Kim; Y H Shin; J E Kim; K S Hwang; J H Choi; M Bahn; Jeong Ju Lee; S H Lee; Y K Bae; J S Lee; J K Choi; Nam-Soon Kim; C Y Yeo; C H Kim
Bibliographic Citation
Scientific Reports, vol. 7, pp. 13278-13278
Publication Year
2017
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.
ISSN
2045-2322
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41598-017-13429-6
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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