Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin

David C. Bowen, Janice Sugiyama, Michael J Ferns, Zach W. Hall

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

During synaptogenesis, agrin, released by motor nerves, causes the clustering of acetylcholine receptors (AChRs) in the skeletal muscle membrane. Although muscle α-dystroglycan has been postulated to be the receptor for the activity of agrin, previous experiments have revealed a discrepancy between the biological activity of soluble fragments of two isoforms of agrin produced by nerves and muscles, respectively, and their ability to bind α-dystroglycan. We have determined the specificity of the signaling receptor by investigating whether muscle agrin can block the activity of neural agrin on intact C2 myotubes. We find that a large excess of muscle agrin failed to inhibit either the number of AChR clusters or the phosphorylation of the AChR induced by picomolar concentrations of neural agrin. These results indicate that neural, but not muscle, agrin interacts with the signaling receptor. Muscle agrin did block the binding of neural agrin to isolated α-dystroglycan, however, suggesting either that α- dystroglycan is not the signaling receptor or that its properties in the membrane are altered. Direct assay of the binding of muscle or neural agrin to intact myotubes revealed only low-affinity binding. We conclude that the signaling receptor for agrin is a high-affinity receptor that is highly specific for the neural form.

Original languageEnglish (US)
Pages (from-to)3791-3797
Number of pages7
JournalJournal of Neuroscience
Volume16
Issue number12
StatePublished - 1996
Externally publishedYes

Fingerprint

Agrin
Muscle Cells
Muscles
Dystroglycans
Cholinergic Receptors
Skeletal Muscle Fibers
Membranes
Cluster Analysis
Protein Isoforms
Skeletal Muscle

Keywords

  • acetylcholine receptor
  • agrin
  • dystroglycan
  • muscle
  • receptor
  • synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin. / Bowen, David C.; Sugiyama, Janice; Ferns, Michael J; Hall, Zach W.

In: Journal of Neuroscience, Vol. 16, No. 12, 1996, p. 3791-3797.

Research output: Contribution to journalArticle

Bowen, David C. ; Sugiyama, Janice ; Ferns, Michael J ; Hall, Zach W. / Neural agrin activates a high-affinity receptor in C2 muscle cells that is unresponsive to muscle agrin. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 12. pp. 3791-3797.
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