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Journal of Neuroscience, Vol 8, 932-944, Copyright © 1988 by Society for Neuroscience
A synapse-specific carbohydrate at the neuromuscular junction: association with both acetylcholinesterase and a glycolipid
LJ Scott, F Bacou and JR Sanes
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110.
With the aim of investigating the roles of carbohydrates in synapse
formation, we have characterized a synapse-specific saccharide at the
vertebrate neuromuscular junction. Two lectins of similar specificity
(Dolichos biflorus agglutinin, DBA, and Vicia villosa-B4 agglutinin,
VVA-B4) stain synaptic but not extrasynaptic regions of the rat muscle
fiber surface and thus define a synapse-specific carbohydrate. Using these
and other probes, we show that the carbohydrate moiety concentrated at the
neuromuscular junction resembles N- acetylgalactosamine (GalNAc) linked in
the beta-anomeric form to the termini of oligosaccharides. VVA-B4 also
selectively stains neuromuscular junctions in human, mouse, rabbit, guinea
pig, chick, frog, axolotl, snake, fish, and lamprey muscles, a phylogenetic
conservatism that suggests a synapse-related role for GalNAc beta- terminal
saccharides. AChE from muscle binds to DBA- and VVA-B4- agarose, and is
thereby identified as a glycoconjugate bearing the synapse-specific
carbohydrate. Assay of AChE isoforms reveals that asymmetric,
collagen-tailed forms, known to be highly concentrated at the rat
neuromuscular junction, bind DBA and VVA-B4, while globular forms, which
are more widely distributed, do not. A second class of GalNAc-bearing
glycoconjugates is demonstrable immunohistochemically with monoclonal
antibodies to stage-specific embryonic antigen (SSEA)-3 (Shevinsky et al.,
1982) and GM2 (Natoli et al., 1986), which recognize GalNAc-bearing
glycolipids. These antibodies selectively stain neuromuscular junctions,
where they recognize glycolipid-like molecules that bind VVA-B4 but are
distinguishable from AChE. The association of a synapse-specific
carbohydrate with at least 2 different synapse- specific molecules raises
the possibility that the former plays a role in determining a property that
the latter share, such as concentration at the synapse.
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