Alpha-galactosidase stimulates acetylcholine receptor aggregation in skeletal muscle cells via PNA-binding carbohydrates.
Aggregation of nicotinic acetylcholine receptors (AChRs) in skeletal muscle is an essential step in the formation of the mammalian neuromuscular junction. While proteins that bind to myotube receptors such as agrin and laminin can stimulate AChR aggregation in cultured myotubes, removal of cell surface sialic acids stimulates aggregation in a ligand-independent manner. Here, we show that removal of cell surface alpha-galactosides also stimulates AChR aggregation in the absence of added laminin or agrin. AChR aggregation stimulated by alpha-galactosidase was blocked by peanut agglutinin (PNA), which binds to lactosamine-containing disaccharides, but not by the GalNAc-binding lectin Vicia villosa agglutinin (VVA-B4). AChR aggregation stimulated by alpha-galactosidase potentiated AChR clustering induced by either neural agrin or laminin-1 and could be inhibited by muscle agrin. These data suggest that capping of cell surface lactosamines or N-acetyllactosamines with alpha-galactose affects AChR aggregation much as capping with sialic acids does.
Parkhomovskiy
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Department of Neurosciences, School of Medicine, University of California, 9500 Gilman Drive, San Diego, California 92093-0691, USA.
Martin
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PT
D000116:Acetylgalactosamine; D018171:Agrin / Q000494:pharmacology; D000606:Amino Sugars; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D004187:Disaccharides; D037102:Lectins / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000502:physiology*; D019887:Peanut Agglutinin / Q000494:pharmacology*; D037121:Plant Lectins; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000519:alpha-Galactosidase / Q000378:metabolism*
D018171:Agrin; D000606:Amino Sugars; D004187:Disaccharides; D037102:Lectins; D019887:Peanut Agglutinin; D037121:Plant Lectins; D011950:Receptors, Cholinergic; C042242:Vicia lectins; C032233:lactosamine; D000519:alpha-Galactosidase; D000116:Acetylgalactosamine