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The retromer complex safeguards against neural progenitor-derived tumorigenesis by regulating Notch receptor

Bo Li1, Chouin Wong1, Shihong Max Gao1

  • 1Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing, China.

Elife
|September 5, 2018
PubMed

Insights

The retromer complex prevents harmful Notch signaling by regulating its trafficking in Drosophila stem cells. Retromer dysfunction leads to aberrant Notch activation and brain tumor formation.

Area of Science:

  • Cell biology
  • Developmental biology
  • Neuroscience

Background:

  • Unidirectional Notch signaling is vital for stem cell homeostasis.
  • Mechanisms preventing ectopic Notch activation and aberrant cell fate are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating Notch receptor trafficking.
  • To investigate the role of the retromer complex in preventing aberrant Notch signaling.

Main Methods:

  • Utilized Drosophila neuroblast lineages as a model system.
  • Investigated Notch polyubiquitination and endosomal trafficking.
  • Analyzed the effects of retromer dysfunction on Notch signaling and cell fate.

Main Results:

  • The retromer complex directly regulates Notch receptor retrograde trafficking in Drosophila neuroblasts.
  • Retromer dysfunction causes accumulation of hypo-ubiquitinated Notch in enlarged endosomes.
  • Aberrant Notch activation in endosomes leads to progenitor dedifferentiation and tumorigenesis.

Conclusions:

  • Retromer acts as a safeguard by retrieving potentially harmful Notch receptors.
  • This mechanism prevents aberrant Notch activation, neural progenitor dedifferentiation, and brain tumor formation.
Keywords:
D. melanogasterneural stem cellneuroblastneurosciencenotch traffickingprogenitor dedifferentiationregenerative medicineretromerstem cellstumorigenesis

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