Acetylcholine receptor clustering associates with proteoglycan biosynthesis in C2 variant and heterkaryon muscle cells

Inhee Mook-Jung, Herman Gordon

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Several lines of evidence have suggested roles for proteoglycans (PGs) in acetylcholine receptor (AChR) clustering on muscle cells. One line of evidence comes from the correlation between a defect in the biosynthesis of glycosaminoglycans (GAGs), the defining carbohydrates of PGs, and the failure of spontaneous AChR clustering in the S27 cell line, a genetic variant of the C2 muscle cell line. Two approaches were used in the present study to investigate whether GAG and AChR clustering defects are causally linked. First, the formation of AChR clusters was examined in two more variant lines, S11 and S26, also isolated from the C2 muscle cell line on the basis of deficiencies in GAG biosynthesis. S11 and S26, like S27, are also defective in AChR clustering. Ion exchange analysis of the GAGs made by the S11, S26, and N27 lines revealed that the defects in GAG biosynthesis differ between the three lines. Second, heterokaryon myotubes formed between pairs of the GAG defective variants were tested for complementation in both AChR clustering and GAG biosynthesis. AChR clusters were conspicuous on individual heterokaryon myotubes, and GAG biosynthesis was restored to near wild type levels in the heterokaryon cultures. Complementation in GAG biosynthesis corroborates the biochemical data that the relevant mutations in the genetic variants are in different genes and establishes that the defects are not dominant. The consistent correlation between GAG defects and the failure of AChR clustering across three independent genetic variants and the complementary association of GAG biosynthesis, with AChR clustering in heterokaryon myotubes argues against a chance association of the two phenotypes and for a causal relationship between PGs and AChR clustering. A prominent chondroitin sulfate peak correlated with AChR clustering in the heterokaryon cultures. This is consistent with earlier results suggesting that chondroitin sulfate in general is required for the spontaneous clustering of AChRs in C2 cultures and further suggests that a particular chondroitin sulfate proteoglycan may be essential for the clustering process.

Original languageEnglish (US)
Pages (from-to)210-218
Number of pages9
JournalJournal of Neurobiology
Volume31
Issue number2
DOIs
StatePublished - Oct 1996

Fingerprint

Cholinergic Receptors
Proteoglycans
Muscle Cells
Glycosaminoglycans
Cluster Analysis
Skeletal Muscle Fibers
Chondroitin Sulfates
Cell Line
Chondroitin Sulfate Proteoglycans
Ion Exchange
Carbohydrates
Phenotype
Mutation

Keywords

  • acetylcholine receptor
  • chondroitin sulfate
  • clustering
  • glycosaminoglycan
  • proteoglycan
  • synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acetylcholine receptor clustering associates with proteoglycan biosynthesis in C2 variant and heterkaryon muscle cells. / Mook-Jung, Inhee; Gordon, Herman.

In: Journal of Neurobiology, Vol. 31, No. 2, 10.1996, p. 210-218.

Research output: Contribution to journalArticle

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