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

Funding Information:
We thank B. Jones, M. Freeman, O. Schuldiner, Y. Nakanishi, U. Gaul, the Developmental Studies Hybridoma Bank, and the Bloomington Stock Center for generously providing fly strains and antibodies. We thank M. Choder and T. Schultheiss for comments on the manuscript and members of the Kurant laboratory for constructive criticism and support. We also thank E. Suss-Toby and L. Liba at the Interdepartmental Bioimaging facility for excellent technical support. We gratefully acknowledge financial support from the Israel Science Foundation (grant 1872/15 ).

Publisher Copyright:
© 2019 The Authors


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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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