Ottogi Inhibits Wnt/β-catenin Signaling by Regulating Cell Membrane Trafficking of Frizzled8. Sci Rep 2017 Oct 16;7(1):13278
Date
10/19/2017Pubmed ID
29038508Pubmed Central ID
PMC5643531DOI
10.1038/s41598-017-13429-6Scopus ID
2-s2.0-85031779920 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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.
Author List
Kim HT, Lee MS, Jeong YM, Ro H, Kim DI, Shin YH, Kim JE, Hwang KS, Choi JH, Bahn M, Lee JJ, Lee SH, Bae YK, Lee JS, Choi JK, Kim NS, Yeo CY, Kim CHAuthor
Sang H. Lee PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Membrane
DNA, Complementary
Embryonic Development
Endoplasmic Reticulum
Gene Expression
Gene Expression Profiling
Gene Expression Regulation, Developmental
Glycosylation
Humans
Phenotype
Protein Binding
Protein Transport
Receptors, Cell Surface
Transcriptome
Wnt Signaling Pathway
Zebrafish Proteins
