Acetylcholine receptor clustering associates with proteoglycan biosynthesis in C2 variant and heterkaryon muscle cells
✍ Scribed by Mook-Jung, Inhee ;Gordon, Herman
- Book ID
- 102655477
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 785 KB
- Volume
- 31
- Category
- Article
- ISSN
- 0022-3034
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✦ Synopsis
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, Sl1 and S26, also isolated from the C2 muscle cell line on the basis of deficiencies in GAG biosynthesis. SI 1 and S26, like S27, are also defective in AChR clustering. Ion exchange analysis of the GAGs made by the S l l , S26, and S27 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 heterokarjon myotubes, and GAG biosynthesis was restored to near wild type lcvels in the heterokaryon cultures. Complementation in GAG hiosynthesis 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 complementarj association of GAG biosynthesis with AChR clustering in heterokaryon myotubes argues against a chance association of the two phenotjpes and for a causal relationship between PGs and AChR clustering. A prominent chondroitin sulfate peak correlated with AChR clustering in the heterokarqon 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 proteoglqcan may be essential for the clustering process.