Literature DB >> 18510933

The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions.

David J Simon1, Jon M Madison, Annie L Conery, Katherine L Thompson-Peer, Michael Soskis, Gary B Ruvkun, Joshua M Kaplan, John K Kim.   

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.

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Year:  2008        PMID: 18510933      PMCID: PMC2553566          DOI: 10.1016/j.cell.2008.04.035

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  48 in total

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