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

Hyun Taek Kim, Mi Sun Lee, Yun Mi Jeong, Hyunju Ro, Dong Il Kim, Yong Hwan Shin, Ji Eun Kim, Kyu Seok Hwang, Jung Hwa Choi, Minjin Bahn, Jeong Ju Lee, Sang H. Lee, Young Ki Bae, Jin Soo Lee, Joong Kook Choi, Nam Soon Kim, Chang Yeol Yeo, Cheol Hee Kim

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2 Scopus citations

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.

Original languageEnglish
Article number13278
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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