Spatial restriction of AChR gene expression to subsynaptic nuclei

Alex Simon, Peter Hoppe, Steven J. Burden

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Acetylcholine receptors (AChRs) and the mRNAs encoding the four AChR subunits are highly concentrated in the synaptic region of skeletal myofibers. The initial localization of AChRs to synaptic sites is triggered by the nerve and is caused, in part, by post-translational mechanisms that involve a redistribution of AChR protein in the myotube membrane. We have used transgenic mice that harbor a gene fusion between the murine AChR delta subunit gene and the human growth hormone gene to show that innervation also activates two independent transcriptional pathways that are important for establishing and maintaining this non-uniform distribution of AChR mRNA and protein. One pathway is triggered by signal(s) that are associated with myofiber depolarization, and these signals act to repress delta subunit gene expression in nuclei throughout the myofiber. Denervation of muscle removes this repression and causes activation of delta subunit gene expression in nuclei in non-synaptic regions of the myofiber. A second pathway is triggered by an unknown signal that is associated with the synaptic site, and this signal acts locally to activate delta subunit gene expression only in nuclei within the synaptic region. Synapse-specific expression, however, does not depend upon the continu-ous presence of the nerve, since transcriptional activation of the delta subunit gene in subsynaptic nuclei persists after denervation. Thus, the nuclei in the synaptic region of multinucleated skeletal myofibers are transcriptionally distinct from nuclei elsewhere in the myofiber, and this spatially restricted transcription pattern is presumably imposed initially by the nerve.

Original languageEnglish (US)
Pages (from-to)545-553
Number of pages9
JournalDevelopment
Volume114
Issue number3
StatePublished - Mar 1992
Externally publishedYes

Fingerprint

Cholinergic Receptors
Gene Expression
Muscle Denervation
Genes
Messenger RNA
Human Growth Hormone
Gene Fusion
Skeletal Muscle Fibers
Denervation
Synapses
Transgenic Mice
Transcriptional Activation
Proteins
Membranes

Keywords

  • Human growth hormone
  • Neuromuscular synapse
  • Synaptic development
  • Transgenic mice

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Simon, A., Hoppe, P., & Burden, S. J. (1992). Spatial restriction of AChR gene expression to subsynaptic nuclei. Development, 114(3), 545-553.

Spatial restriction of AChR gene expression to subsynaptic nuclei. / Simon, Alex; Hoppe, Peter; Burden, Steven J.

In: Development, Vol. 114, No. 3, 03.1992, p. 545-553.

Research output: Contribution to journalArticle

Simon, A, Hoppe, P & Burden, SJ 1992, 'Spatial restriction of AChR gene expression to subsynaptic nuclei', Development, vol. 114, no. 3, pp. 545-553.
Simon, Alex ; Hoppe, Peter ; Burden, Steven J. / Spatial restriction of AChR gene expression to subsynaptic nuclei. In: Development. 1992 ; Vol. 114, No. 3. pp. 545-553.
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