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Cell ; 133(5): 903-15, 2008 May 30.
Article in English | MEDLINE | ID: mdl-18510933

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.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , MicroRNAs/metabolism , Neuromuscular Junction/metabolism , Signal Transduction , Transcription Factors/metabolism , Animals , Levamisole/pharmacology , MicroRNAs/genetics , Mutation , Nicotinic Agonists/metabolism , Receptors, Nicotinic/metabolism , Transcription, Genetic , rab3 GTP-Binding Proteins/metabolism
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