JNK pathway activation is able to synchronize neuronal death and glial phagocytosis in Drosophila

J. Shklover, K. Mishnaevski, F. Levy-Adam, E. Kurant

Research output: Contribution to journalArticlepeer-review

Abstract

Glial phagocytosis of superfluous neurons and damaged or aberrant neuronal material is crucial for normal development and maintenance of the CNS. However, the molecular mechanisms underlying the relationship between neuronal death and glial phagocytosis are poorly understood. We describe a novel mechanism that is able to synchronize neuronal cell death and glial phagocytosis of dying neurons in the Drosophila embryonic CNS. This mechanism involves c-Jun N-terminal kinase (JNK) signaling, which is required for developmental apoptosis of specific neurons during embryogenesis. We demonstrate that the dJNK pathway gain-of-function in neurons leads to dJNK signaling in glia, which results in upregulation of glial phagocytosis. Importantly, this promotion of phagocytosis is not mediated by upregulation of the glial phagocytic receptors SIMU and DRPR, but by increasing glial capacity to degrade apoptotic particles inside phagosomes. The proposed mechanism may be important for removal of damaged neurons in the developing and mature CNS.

Original languageEnglish
Article numbere1649
JournalCell Death and Disease
Volume6
Issue number2
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgements. We would like to thank B Jones, O Schuldiner, D Bohmann, E Arama, M Freeman, A Salzberg, Hybridoma bank and the Bloomington Stock Center for generously providing fly strains and antibodies. We thank A Salzberg and T Schultheiss for comments on the manuscript, and the Kurant laboratory members for constructive criticism and support. We also thank E Suss-Toby at the Interdepartmental Bioimaging facility for excellent technical support. We gratefully acknowledge financial support from the Israel Science Foundation (grant no 427/11) and from Allen and Jewell Prince Center for Neurodegenerative Disorders of the Brain.

Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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