The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions.
basic_science · Level V
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- Record sourced from PubMed, PMID 18510933.
- Also identified by DOI 10.1016/j.cell.2008.04.035 and PMC identifier 2553566.
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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.
Medical subject headings
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- MicroRNAs
- Neuromuscular Junction
- Signal Transduction
- Transcription Factors