A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

TY - JOUR

T1 - A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate

AU - Aw, Sherry Shiying

AU - Lim, Isaac Kok Hwee

AU - Tang, Melissa Xue Mei

AU - Cohen, Stephen Michael

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/5/30

Y1 - 2017/5/30

N2 - Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is known about their function, and the effects of their misregulation, in these non-neuronal cells. Here, we report a glio-protective role for Drosophila mir-263a mediated by its regulation of glutamate receptor levels in glia. mir-263a mutants exhibit a pronounced movement defect due to aberrant overexpression of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment.

AB - Glutamate is a ubiquitous neurotransmitter, mediating information flow between neurons. Defects in the regulation of glutamatergic transmission can result in glutamate toxicity, which is associated with neurodegeneration. Interestingly, glutamate receptors are expressed in glia, but little is known about their function, and the effects of their misregulation, in these non-neuronal cells. Here, we report a glio-protective role for Drosophila mir-263a mediated by its regulation of glutamate receptor levels in glia. mir-263a mutants exhibit a pronounced movement defect due to aberrant overexpression of CG5621/Grik, Nmdar1, and Nmdar2. mir-263a mutants exhibit excitotoxic death of a subset of astrocyte-like and ensheathing glia in the CNS. Glial-specific normalization of glutamate receptor levels restores cell numbers and suppresses the movement defect. Therefore, microRNA-mediated regulation of glutamate receptor levels protects glia from excitotoxicity, ensuring CNS health. Chronic low-level glutamate receptor overexpression due to mutations affecting microRNA (miRNA) regulation might contribute to glial dysfunction and CNS impairment.

KW - Journal Article

U2 - 10.1016/j.celrep.2017.05.010

DO - 10.1016/j.celrep.2017.05.010

M3 - Journal article

C2 - 28564598

SN - 2639-1856

VL - 19

SP - 1783

EP - 1793

JO - Cell Reports

JF - Cell Reports

IS - 9

ER -