Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8
- 등재 SCIE, SCOPUS
- 발행기관 Nature Publishing Group
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000149601
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s41598-017-13429-6
초록/요약
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).
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