A Glio-Protective Role of mir-263a by Tuning Sensitivity to Glutamate Aw, Sherry Shiying et al. Cell Reports, Volume 19, Issue 9, 1783 - 1793
Abstract:
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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http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
We thank Kah Junn Tan and Alice Liu for technical support and members of the Cohen lab for insightful discussions. We also thank Rolf Bodmer, Chia-Lin Wu, Shouzhen Xia, Marc Freeman, Tzumin Lee, and David Foronda for generously sharing reagents. This work was supported by the Institute of Molecular and Cell Biology, Singapore , by A∗STAR Joint Council Organisation grant 15302FG149 to S.S.A., and by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme (Parkinson’s Disease) grant NMRC/TCR/013-NNI/2014 administered by the Singapore Ministry of Health’s National Medical Research Council. S.M.C. was supported by NovoNordisk Foundation grant NNF12OC0000552 for part of this work.
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