The MicroRNA miR-1 Regulates a MEF-2-Dependent Retrograde Signal at Neuromuscular Junctions

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 sensiti...

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Bibliographic Details
Published in:Cell 2008-05, Vol.133 (5), p.903-915
Main Authors: Simon, David J., Madison, Jon M., Conery, Annie L., Thompson-Peer, Katherine L., Soskis, Michael, Ruvkun, Gary B., Kaplan, Joshua M., Kim, John K.
Format: Article
Language:English
Subjects:
Animals
Caenorhabditis elegans - metabolism
Caenorhabditis elegans Proteins - metabolism
Levamisole - pharmacology
MicroRNAs - genetics
MicroRNAs - metabolism
MOLNEURO
Mutation
Neuromuscular Junction - metabolism
Nicotinic Agonists - metabolism
rab3 GTP-Binding Proteins - metabolism
Receptors, Nicotinic - metabolism
RNA
Signal Transduction
SIGNALING
Transcription Factors - metabolism
Transcription, Genetic
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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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2008.04.035