Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain

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

doi:10.1016/j.celrep.2019.09.086

Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain

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

Department of Human Biology

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English
Pages (from-to)	1438-1448.e3
Journal	Cell Reports
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.celrep.2019.09.086
State	Published - 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

Keywords

CNS
Draper
Drosophila
SIMU
glia
neurodegeneration
phagocytosis
phagoptosis
phosphatidylserine

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (all)

Access to Document

10.1016/j.celrep.2019.09.086

Cite this

@article{04ca6546ebde4d28abcc4d55af26b566,

title = "Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain",

abstract = "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.",

keywords = "CNS, Draper, Drosophila, SIMU, glia, neurodegeneration, phagocytosis, phagoptosis, phosphatidylserine",

author = "Ketty Hakim-Mishnaevski and Naama Flint-Brodsly and Boris Shklyar and Flonia Levy-Adam and Estee Kurant",

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: {\textcopyright} 2019 The Authors",

year = "2019",

month = nov,

day = "5",

doi = "10.1016/j.celrep.2019.09.086",

language = "English",

volume = "29",

pages = "1438--1448.e3",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain

AU - Hakim-Mishnaevski, Ketty

AU - Flint-Brodsly, Naama

AU - Shklyar, Boris

AU - Levy-Adam, Flonia

AU - Kurant, Estee

N1 - 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

PY - 2019/11/5

Y1 - 2019/11/5

N2 - 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.

AB - 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.

KW - CNS

KW - Draper

KW - Drosophila

KW - SIMU

KW - glia

KW - neurodegeneration

KW - phagocytosis

KW - phagoptosis

KW - phosphatidylserine

UR - http://www.scopus.com/inward/record.url?scp=85074293595&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2019.09.086

DO - 10.1016/j.celrep.2019.09.086

M3 - Article

C2 - 31693886

AN - SCOPUS:85074293595

SN - 2211-1247

VL - 29

SP - 1438-1448.e3

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this