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Cell. 2008 May 30;133(5):903-15. doi: 10.1016/j.cell.2008.04.035.

The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions.

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  • 1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

We show that miR-1, a conserved muscle-specific microRNA, regulates aspects of both pre- and postsynaptic function at C. elegans neuromuscular junctions. miR-1 regulates the expression level of two nicotinic acetylcholine receptor (nAChR) subunits (UNC-29 and UNC-63), thereby altering muscle sensitivity to acetylcholine (ACh). miR-1 also regulates the muscle transcription factor MEF-2, which results in altered presynaptic ACh secretion, suggesting that MEF-2 activity in muscles controls a retrograde signal. The effect of the MEF-2-dependent retrograde signal on secretion is mediated by the synaptic vesicle protein RAB-3. Finally, acute activation of levamisole-sensitive nAChRs stimulates MEF-2-dependent transcriptional responses and induces the MEF-2-dependent retrograde signal. We propose that miR-1 refines synaptic function by coupling changes in muscle activity to changes in presynaptic function.

PMID:
18510933
[PubMed - indexed for MEDLINE]
PMCID:
PMC2553566
Free PMC Article

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