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Overexpressed Gliotactin activates BMP signaling through interfering with the Tkv–Dad association
- 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.
- Subjects :
- 0301 basic medicine
animal structures
Nerve Tissue Proteins
Receptors, Cell Surface
Protein Serine-Threonine Kinases
Biology
Endocytosis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Genetics
Animals
Drosophila Proteins
RNA, Messenger
Receptor
BMP signaling pathway
Molecular Biology
Messenger RNA
Membrane Proteins
Tyrosine phosphorylation
Cell migration
General Medicine
Cell biology
MicroRNAs
Drosophila melanogaster
030104 developmental biology
chemistry
Apoptosis
Bone Morphogenetic Proteins
Ectopic expression
030217 neurology & neurosurgery
Signal Transduction
Biotechnology
Subjects
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