Activity-Dependent Pre-miR-134 Dendritic Localization Is Required for Hippocampal Neuron Dendritogenesis

Open access
Date
2018-06-11Type
- Journal Article
Citations
Cited 16 times in
Web of Science
Cited 16 times in
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ETH Bibliography
yes
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Abstract
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 activitydependent 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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000271468Publication status
publishedExternal links
Journal / series
Frontiers in Molecular NeuroscienceVolume
Pages / Article No.
Publisher
FrontiersSubject
dendritogenesis; microRNA; neuronal activity; BDNF; NMDA receptor; RNA transport; neuronal developmentOrganisational unit
09498 - Schratt, Gerhard / Schratt, Gerhard
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Show all metadata
Citations
Cited 16 times in
Web of Science
Cited 16 times in
Scopus
ETH Bibliography
yes
Altmetrics