Synapse-specific gene expression at the neuromuscular junction.

Full Abstract

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 delta and epsilon gene transcription to the skeletal muscle subsynaptic area was identified. This element, named N-box, recruits the Ets-related transcription factor GABP to AChR delta and epsilon 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 epsilon gene promoter and showing reduced levels of AChR epsilon 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.

Author information

Author/s: Méjat, Alexandre (A); Ravel-Chapuis, Aymeric (A); Vandromme, Marie (M); Schaeffer, Laurent (L);

Affiliation: Equipe Différenciation Neuromusculaire, UMR 5161 CNRS/ENS, Ecole Normale Supérieure de Lyon, Lyon, France.

Journal and publication information

Publication Type: Journal Article; Review

Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci), published in United States. (Language: eng)

Reference: 2003-Sep; vol 998 (issue ) : pp 53-65

Dates: Created 2003/10/31; Completed 2003/12/01; Revised 2008/11/21;

PMID: 14592863, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: 18 Feb 2009 00:00:00)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Associated Chemicals: Agrin (0) ; DNA-Binding Proteins (0) ; Membrane Proteins (0) ; Neuregulins (0) ; Receptors, Cholinergic (0) ; Transcription Factors (0) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; MUSK protein, human (EC 2.7.10.1)

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