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

Title
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.
Ewha Authors
여창열
SCOPUS Author ID
여창열scopus
Issue Date
2017
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 7, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2017 The Author(s).
DOI
10.1038/s41598-017-13429-6
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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