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Synapse‐Specific Gene Expression at the Neuromuscular Junction
Author(s) -
MÉJAT ALEXANDRE,
RAVELCHAPUIS AYMERIC,
VANDROMME MARIE,
SCHAEFFER LAURENT
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1254.008
Subject(s) - synapse , neuromuscular junction , neuroscience , gene , gene expression , microbiology and biotechnology , biology , genetics
A bstract : 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 δ and ε gene transcription to the skeletal muscle subsynaptic area was identified. This element, named N‐box, recruits the Ets‐related transcription factor GABP to AChR δ and ε 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 ε gene promoter and showing reduced levels of AChR ε 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.