Core Concepts
The E3 ubiquitin ligase Deltex (Dx) regulates Wingless (Wg) signaling in Drosophila by facilitating the spreading of the Wg gradient and promoting the proteasomal degradation of the Wg effector Armadillo/β-catenin.
Abstract
The study investigates the role of the E3 ubiquitin ligase Deltex (Dx) in the regulation of Wingless (Wg) signaling in Drosophila. The key findings are:
Dx genetically interacts with components of the Wg signaling pathway, including the Wg ligand, its receptor Frizzled, and the transcriptional effector Armadillo (Arm).
Loss of Dx reduces the Wg gradient and the expression of Wg target genes, while overexpression of Dx expands the Wg gradient and affects the expression of short-range and long-range Wg targets.
Dx facilitates the endocytosis and trafficking of Wg, which contributes to the regulation of the Wg gradient.
Dx directly interacts with and promotes the proteasomal degradation of Arm, the Drosophila homolog of β-catenin, a key effector of Wg signaling.
The human homolog of Dx, DTX1, also binds to and facilitates the degradation of β-catenin, suggesting a conserved mechanism of Wg/Wnt signaling regulation.
The study highlights the multifaceted role of Dx in modulating Wg signaling, both at the level of Wg gradient formation and Arm/β-catenin stability, thereby providing insights into the regulation of this crucial developmental signaling pathway.
Stats
Dx overexpression with en-GAL4 results in a significant reduction in the expression of the Wg target genes Senseless and Cut.
Dx overexpression with en-GAL4 leads to a marked decrease in the accumulation of the Wg effector Armadillo (Arm) in the wing imaginal disc.
Proteasome inhibitor MG132 treatment rescues the Dx-mediated downregulation of Arm in wing imaginal discs.
Overexpression of Dx in HEK-293 cells leads to a reduction in the levels of β-catenin, which is rescued by MG132 treatment.
Quotes
"Dx over-expression with en-GAL4 shows pupal lethality at 25°C, however, at 18°C, the flies emerge with massive morphological defects."
"Dx over-expression in the thorax leads to reduced and disoriented macrochaetae and reduction in scutellar bristles."
"Dx over-expression in the leg results in a reduced tarsal segment along the proximodistal axis and dorsoventral shift of the sex combs."