RRC ID |
4297
|
Author |
Simon DJ, Madison JM, Conery AL, Thompson-Peer KL, Soskis M, Ruvkun GB, Kaplan JM, Kim JK.
|
Title |
The microRNA miR-1 regulates a MEF-2-dependent retrograde signal at neuromuscular junctions.
|
Journal |
Cell
|
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.
|
Volume |
133(5)
|
Pages |
903-15
|
Published |
2008-5-30
|
DOI |
10.1016/j.cell.2008.04.035
|
PII |
S0092-8674(08)00609-0
|
PMID |
18510933
|
PMC |
PMC2553566
|
MeSH |
Animals
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / metabolism*
Levamisole / pharmacology
MicroRNAs / genetics
MicroRNAs / metabolism*
Mutation
Neuromuscular Junction / metabolism*
Nicotinic Agonists / metabolism
Receptors, Nicotinic / metabolism
Signal Transduction*
Transcription Factors / metabolism*
Transcription, Genetic
rab3 GTP-Binding Proteins / metabolism
|
IF |
38.637
|
Times Cited |
135
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
Resource |
C.elegans |
tm1635 |