Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain

Ketty Hakim-Mishnaevski, Naama Flint-Brodsly, Boris Shklyar, Flonia Levy-Adam, Estee Kurant

Research output: Contribution to journalArticlepeer-review


Glial phagocytosis is critical for the development and maintenance of the CNS in vertebrates and flies and relies on the function of phagocytic receptors to remove apoptotic cells and debris. Glial phagocytic ability declines with age, which correlates with neuronal dysfunction, suggesting that increased glial phagocytosis may prevent neurodegeneration. Contradicting this hypothesis, we provide experimental evidence showing that an elevated expression of the phagocytic receptors Six-Microns-Under (SIMU) and Draper (Drpr) in adult Drosophila glia leads to a loss of both dopaminergic and GABAergic neurons, accompanied by motor dysfunction and a shortened lifespan. Importantly, this reduction in neuronal number is not linked to neuronal apoptosis, but rather to phosphatidylserine-mediated phagoptosis of live neurons by hyper-phagocytic glia. Altogether, our study reveals that the level of glial phagocytic receptors must be tightly regulated for proper brain function and that neurodegeneration occurs not only by defective, but also excessive glial cell function.

Original languageEnglish
Pages (from-to)1438-1448.e3
JournalCell Reports
Issue number6
StatePublished - 5 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors


  • CNS
  • Draper
  • Drosophila
  • SIMU
  • glia
  • neurodegeneration
  • phagocytosis
  • phagoptosis
  • phosphatidylserine

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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