Molecular mechanisms mediating synapse-specific gene expression during development of the neuromuscular junction.
Can J Appl Physiol
; 23(4): 390-5, 1998 Aug.
Article
in En
| MEDLINE
| ID: mdl-9677435
ABSTRACT
Adult skeletal muscle locally expresses nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction by selective induction of their subunit-encoding genes (alpha beta epsilon delta) in endplate-associated myonuclei. Neuregulin/ARIA is a nerve-derived factor that is thought to be largely responsible for this local gene induction. Neuregulin/ARIA activates a Ras/MAP kinase signalling cascade, which ultimately induces nAChR epsilon-subunit gene expression via a 15 bp sequence that harbors a core Ets transcription factor binding site (GGA). Interestingly, this same sequence also appears to participate in extrajunctional repression of the epsilon-subunit gene. Muscle Ets 2 overexpression induces nAChR epsilon-subunit gene promoter activity, whereas a dominant/negative Ets blocks neuregulin-dependent induction. These results suggest that Ets transcription factors play a role in mediating synapse-specific and neuregulin-mediated motor neuron control of nAChR gene expression.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Synapses
/
Gene Expression Regulation
/
Neuromuscular Junction
Limits:
Adult
/
Humans
Language:
En
Journal:
Can J Appl Physiol
Journal subject:
FISIOLOGIA
/
MEDICINA ESPORTIVA
Year:
1998
Document type:
Article
Affiliation country:
United States