Journal
FRONTIERS IN MOLECULAR NEUROSCIENCE
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fnmol.2018.00171
Keywords
dendritogenesis; microRNA; neuronal activity; BDNF; NMDA receptor; RNA transport; neuronal development
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Funding
- Deutsche Forschungsgemeinschaft [DFG SCHR 1136/8-1, 1136/4-1]
- Von Behring-Rontgen-Foundation [62-0004]
- University Medical Center Giessen and Marburg (UKGM) [7/2015 MR]
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microRNAs (miRNAs) have emerged as critical regulators of neuronal dendrite development. Specific precursor (pre-) miRNAs are actively transported to dendrites, but whether this process is regulated by neuronal activity and involved in activity-dependent dendritogenesis is unknown. Here we show that BDNF, a neurotrophin that is released in response to increased neuronal activity, promotes dendritic accumulation of pre-miR-134. Dendritic accumulation, but not transcription of pre-miR-134, is abrogated by treatment of neurons with the NMDA receptor (NMDAR) antagonist APV. Furthermore, APV interferes with BDNF-mediated repression of the known miR-134 target Pumilio 2 (Pum2) in a miR-134 binding site-specific manner. At the functional level, both APV treatment and knockdown of the pre-miR-134 transport protein DHX36 antagonize BDNF-induced dendritogenesis. These effects are likely mediated by reduced dendritic miR-134 activity, since both transfection of a synthetic miR-134 duplex or of a dendritically targeted pre-miR-134-181a chimera rescues BDNF-dependent dendritogenesis in the presence of APV. In conclusion, we have identified a novel NMDAR-dependent mechanism involved in the activity-dependent control of miRNA function during neuronal development.
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