RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes

Michael J Ferns, Werner Hoch, James T. Campanelli, Fabio Rupp, Zach W. Hall, Richard H. Scheller

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

Agrin is a component of the synaptic basal lamina that induces the clustering of acetylcholine receptors (AChRs) on muscle fibers. A region near the carboxyl terminus of the protein exists in four forms that are generated by alternative RNA splicing. All four alternatively spliced forms of agrin are active in inducing AChR clusters on rat primary and C2-derived muscle fibers. In contrast, only two forms of the protein, each containing an 8 amino acid insert, are capable of inducing clusters on myotubes of S27 cells, a C2 variant that has defective proteoglycans. These two forms are also most active in inducing clusters on chick myotubes. This pattern of differential activity suggests that RNA splicing of agrin transcripts and interactions with proteoglycans or other components of basal lamina have important roles in regulating the localization of neurotransmitter receptors at synaptic sites.

Original languageEnglish (US)
Pages (from-to)1079-1086
Number of pages8
JournalNeuron
Volume8
Issue number6
DOIs
StatePublished - 1992

ASJC Scopus subject areas

  • Neuroscience(all)

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