α-Dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin-MuSK signaling

Christian Jacobson, Federica Montanaro, Michael Lindenbaum, Salvatore Carbonetto, Michael J Ferns

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

α-dystroglycan (α-DG) is an agrin-binding protein that has been implicated in acetylcholine receptor (AChR) clustering, but it is unclear whether it acts as a coreceptor involved in initial agrin signaling or as a component involved in later events. To investigate its role, we have generated antisense derivatives of the C2 mouse muscle cell line, which have reduced α-DG expression. When compared with wild-type cells, the α-DG- deficient myotubes have a dramatic reduction in the number of spontaneous and agrin-induced AChR clusters. Several findings suggest that this decrease in AChR clustering is likely not because of a defect in agrin signaling through the MuSK receptor tyrosine kinase. Compared with wild-type cells, the α-DG- deficient cell lines showed only a transient reduction in the level of agrin- induced MuSK tyrosine phosphorylation and no reduction in AChR β-subunit tyrosine phosphorylation. Additionally, agrin-induced phosphorylation of MuSK in wild-type myotubes was not decreased using agrin fragments that lack the domain primarily responsible for binding to α-DG. Finally, neural agrin- induced phosphorylation of MuSK was unaffected by treatments such as excess muscle agrin or antiα-DG antibodies, both of which block agrin-α-DG binding. Together, these results suggest that α-DG is not required for agrin-MuSK signaling but rather that it may play a role elsewhere in the clustering pathway, such as in the downstream consolidation or maintenance of AChR clusters.

Original languageEnglish (US)
Pages (from-to)6340-6348
Number of pages9
JournalJournal of Neuroscience
Volume18
Issue number16
StatePublished - Aug 15 1998
Externally publishedYes

Fingerprint

Agrin
Receptor Aggregation
Dystroglycans
Cholinergic Receptors
Phosphorylation
Cluster Analysis
Skeletal Muscle Fibers
Tyrosine
Cell Line
Receptor Protein-Tyrosine Kinases
Muscle Cells
Anti-Idiotypic Antibodies

Keywords

  • Acetylcholine receptor
  • Agrin
  • Dystroglycan
  • Neuromuscular junction
  • Phosphorylation
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

α-Dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin-MuSK signaling. / Jacobson, Christian; Montanaro, Federica; Lindenbaum, Michael; Carbonetto, Salvatore; Ferns, Michael J.

In: Journal of Neuroscience, Vol. 18, No. 16, 15.08.1998, p. 6340-6348.

Research output: Contribution to journalArticle

Jacobson, C, Montanaro, F, Lindenbaum, M, Carbonetto, S & Ferns, MJ 1998, 'α-Dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin-MuSK signaling', Journal of Neuroscience, vol. 18, no. 16, pp. 6340-6348.
Jacobson, Christian ; Montanaro, Federica ; Lindenbaum, Michael ; Carbonetto, Salvatore ; Ferns, Michael J. / α-Dystroglycan functions in acetylcholine receptor aggregation but is not a coreceptor for agrin-MuSK signaling. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 16. pp. 6340-6348.
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