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Synapse-Specific Gene Expression at the Neuromuscular Junction
Equipe Différenciation Neuromusculaire, UMR 5161 CNRS/ENS, Ecole Normale Supérieure de Lyon, Lyon, France
Address for correspondence: Laurent Schaeffer, Equipe Différenciation Neuromusculaire, UMR 5161 CNRS/ENS, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon cedex 07, France. Voice: +33-472-728-573; fax: +33-472-728-080. lschaeff{at}ens-lyon.fr Ann. N.Y. Acad. Sci. 998: 53-65 (2003).
Agrin is the key neural factor that controls muscle postsynaptic differentiation, including the induction of synapse-specific transcription via neuregulins. In 1995, the promoter element responsible for the targeting of AChR
 and  gene transcription to the skeletal muscle subsynaptic area was identified. This element, named N-box, recruits the Ets-related transcription factor GABP to AChR and promoters, and both the N-box and GABP are required to obtain transcriptional stimulation by neuregulins. The physiological importance of the N-box has been definitively established with the discovery of myasthenic families carrying single-point mutations in the N-box of the AChR gene promoter and showing reduced levels of AChR subunit expression. The control of synapse-specific transcription by agrin and neuregulins through the N-box and GABP is not restricted to the case of AChR genes. The same regulation holds true for the ACh esterase and utrophin genes, thus showing that nerve-induced transcriptional activation of several synapse-specific genes is triggered by a common mechanism involving agrin, neuregulins, and ultimately the N-box and Ets-related transcription factors.
Key Words: neuromuscular junction (NMJ) • acetylcholine receptor (AChR) • transcription • neuregulins • GABP This article has been cited by other articles:
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