Cell
Volume 133, Issue 5, 30 May 2008, Pages 903-915
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Article
The MicroRNA miR-1 Regulates a MEF-2-Dependent Retrograde Signal at Neuromuscular Junctions

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Summary

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.

MOLNEURO
RNA
SIGNALING

Cited by (0)

3

These authors contributed equally to this work.

4

Present address: Life Sciences Institute, Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.

5

Present address: Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.