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Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

The tumour suppressor Lethal (2) giant discs is required for the function of the ESCRT-III component Shrub/CHMP4

Tobias Troost1, Sandra Jaeckel, Nadja Ohlenhard

  • 1Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse1, 40225, Düsseldorf, Germany.

Journal of Cell Science
|March 6, 2012
PubMed

Insights

Defects in the endosomal pathway due to mutations in the lethal (2) giant discs (lgd) gene or ESCRT complexes cause Notch pathway activation in Drosophila. Lgd

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Loss of function in the tumor suppressor gene lethal (2) giant discs (lgd) or ESCRT complexes disrupts late endosomal pathways.
  • This disruption leads to ligand-independent activation of the Notch pathway in Drosophila melanogaster imaginal disc cells.
  • The Lgd protein, containing C2 and DM14 domains, has an uncharacterized function, particularly the DM14 repeats.

Purpose of the Study:

  • To perform a detailed structure-function analysis of the Lgd protein.
  • To elucidate the role of Lgd's C2 and DM14 domains in its function and localization.
  • To investigate the interaction between Lgd and the ESCRT-III complex and its impact on Notch pathway activation.

Main Methods:

  • Structure-function analysis of Lgd protein domains.
  • Investigation of Lgd interaction with ESCRT-III subunit Shrub.
  • Genetic studies to compare Notch activation mechanisms in lgd and ESCRT mutants.

Main Results:

  • The DM14 domains of Lgd are essential and redundant for its function, providing specificity.
  • The C2 domain of Lgd is crucial for its correct subcellular localization.
  • Lgd directly interacts with the ESCRT-III subunit Shrub via its DM14 domains, contributing to ESCRT-III function.

Conclusions:

  • Lgd is a key component of the ESCRT-III complex, essential for its function.
  • The interaction between Lgd and ESCRT-III is vital for regulating the Notch pathway.
  • Notch pathway activation in lgd and ESCRT mutants occurs through distinct mechanisms, with ESCRT components required for Notch activation in lgd mutants.

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