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Title 

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

Authors 

H T KimM S LeeY M JeongH RoD I KimY H ShinJ E KimK S HwangJ H ChoiM BahnJeong Ju LeeS H LeeY K BaeJ S LeeJ K ChoiNam-Soon KimC Y YeoC H Kim

Publisher 

Nature Publishing Group

Issue Date 

2017

Citation 

Scientific Reports

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

Link 

http://dx.doi.org/10.1038/s41598-017-13429-6

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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