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

• Published in: Cell reports (Cambridge) Vol. 19; no. 9; pp. 1783 - 1793
• Main Authors: Aw, Sherry Shiying, Lim, Isaac Kok Hwee, Tang, Melissa Xue Mei, Cohen, Stephen Michael
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-05-2017; Elsevier
• Subjects: Animals; astrocyte; Astrocytes - drug effects; Astrocytes - metabolism; Cell Death - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; climbing defects; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; excitotoxicity; Female; glia; glutamate; Glutamates - metabolism; Glutamic Acid - toxicity; Membrane Potentials - drug effects; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Movement; movement disorder; Mutation - genetics; neurodegeneration; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - pathology; Phenotype; Receptors, Glutamate - metabolism; Signal Transduction - drug effects; movement disorder; climbing defects; Drosophila; neurodegeneration; microRNA; excitotoxicity; glia; astrocyte; glutamate
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.05.010

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.
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•mir-263a mutants exhibit death of a subset of astrocyte-like and ensheathing glia•These defects are associated with severe movement defects•mir-263a regulates glutamate receptor levels to protect glia from excitotoxicity
Excessive glutamatergic signaling can cause neurodegeneration. Aw et al. report that Drosophila mir-263a limits glutamate receptor levels in a subset of glia, protecting them from excitotoxicity. mir-263a mutants exhibit severe movement defects. This study reveals a mechanism by which glia protect themselves from excess glutamate signaling to maintain CNS health.