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 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.
Simon
David J
DJ
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Madison
Jon M
JM
Conery
Annie L
AL
Thompson-Peer
Katherine L
KL
Soskis
Michael
M
Ruvkun
Gary B
GB
Kaplan
Joshua M
JM
Kim
John K
JK
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D007978:Levamisole / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014157:Transcription Factors; C529480:UNC-29 protein, C elegans; C493164:Unc-63 protein, C elegans; C518291:mef-2 protein, C elegans; D007978:Levamisole; D020692:rab3 GTP-Binding Proteins