Modulation of mGluR-dependent MAP1B translation and AMPA receptor endocytosis by microRNA miR-146a-5p.

J Neurosci

Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, Republic of China.

Published: May 2013

The translation of dendritic microtubule-associated protein 1B (MAP1B) is exaggerated upon group I mGluR activation leading to AMPA receptor (AMPAR) endocytosis and consequent long-term depression. However, the mechanisms of regulation of MAP1B protein synthesis in the mature dendrites remain unclear. Here we have identified miR-146a-5p that targets the 3' UTR of MAP1B mRNA and represses its translation. Inhibition of the endogenous miR-146a-5p in mouse cultured hippocampal neurons triggers an increase of the dendritic MAP1B protein as well as the internalization of AMPARs, resulting in a decline in synaptic transmission. Conversely, enforced expression of miR-146a-5p inhibits MAP1B translation and attenuates group I mGluR-induced AMPAR endocytosis. Moreover, siRNA-mediated knockdown of MAP1B recovers the impairment of synaptic transmission caused by inhibition of miR-146a-5p. These results reveal that miR-146a-5p modulates the synaptic plasticity via repression of MAP1B protein synthesis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705019PMC
http://dx.doi.org/10.1523/JNEUROSCI.5210-12.2013DOI Listing

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