Back to Search Start Over

Overexpressed Gliotactin activates BMP signaling through interfering with the Tkv–Dad association

Authors :
Vanessa J. Auld
Zohreh Sharifkhodaei
Source :
Genome. 64:97-108
Publication Year :
2021
Publisher :
Canadian Science Publishing, 2021.

Abstract

Epithelial junctions ensure cell–cell adhesion and establish permeability barriers between cells. At the corners of epithelia, the tricellular junction (TCJ) is formed by three adjacent epithelial cells and generates a functional barrier. In Drosophila, a key TCJ protein is Gliotactin (Gli) where loss of Gli disrupts barrier formation and function. Conversely, overexpressed Gli spreads away from the TCJ and triggers apoptosis, delamination, and cell migration. Thus, Gli protein levels are tightly regulated and by two mechanisms, at the protein levels by tyrosine phosphorylation and endocytosis and at the mRNA level through microRNA-184. Regulation of Gli mRNA is mediated through a Gli–BMP–miR184 feedback loop. Excessive Gli triggers BMP signaling pathway through the activation of Tkv type-I BMP receptor and Mad. Elevated level of pMad induces micrRNA-184 expression which in turn targets the Gli 3′UTR and mRNA degradation. Gli activation of Tkv is not through its ligand Dpp but rather through the inhibition of Dad, an inhibitory-Smad. Here, we show that ectopic expression of Gli interferes with Tkv–Dad association by sequestering Dad away from Tkv. The reduced inhibitory effect of Dad on Tkv results in the increased Tkv–pMad signaling activity, and this effect is continuous through larval and pupal wing formation.

Details

ISSN :
14803321 and 08312796
Volume :
64
Database :
OpenAIRE
Journal :
Genome
Accession number :
edsair.doi.dedup.....cd3790403ff0f43a327d5d4c8888fb80
Full Text :
https://doi.org/10.1139/gen-2020-0026