Gangliosides are neuronal ligands for myelin-associated glycoprotein

Lynda J.S. Yang, Cynthia B. Zeller, Nancy L. Shaper, Makoto Kiso, Akira Hasegawa, Robert E. Shapiro, Ronald L. Schnaar

Research output: Contribution to journalArticle

Abstract

Nerve cells depend on specific interactions with glial cells for proper function. Myelinating glial cells are thought to associate with neuronal axons, in part, via the cell-surface adhesion protein, myelin-associated glycoprotein (MAG). MAG is also thought to be a major inhibitor of neurite outgrowth (axon regeneration) in the adult central nervous system. Primary structure and in vitro function place MAG in an immunoglobulin-related family of sialic acid-binding lectins. We report that a limited set of structurally related gangliosides. known to be expressed on myelinated neurons in vivo, are ligands fur MAG. When major brain gangliosides were adsorbed as artificial membranes on plastic microwells, only GT1b and GD1a supported cell adhesion of MAG-transfected COS-1 cells. Furthermore, a quantitatively minor ganglioside expressed on cholinergic neurons, GQ1bα (also known as Chol- 1α-b). was much more potent than GT1b or GD1a in supporting MAG-mediated cell adhesion. Adhesion to either GT1b or GQ1bα was abolished by pretreatment of the adsorbed gangliosides with neuraminidase. On the basis of structure-function studies of 19 test glycosphingolipids, an α2,3-N- acetylneuraminic acid residue on the terminal galactose of a gangliotetraose core is necessary for MAG binding, and additional sialic acid residues linked to the other neutral cure saccharides [Gal(II)) and GalNAc(III)] contribute significantly to binding affinity. MAG-mediated adhesion to gangliosides was blocked by pretreatment of the MAG-transfected COS-1 cells with anti-MAG monoclonal antibody 513. which is known to inhibit oligodendrocyte-neuron binding. These data are consistent with the conclusion that MAG-mediated cell-cell interactions involve MAG-ganglioside recognition and binding.

Original languageEnglish (US)
Pages (from-to)814-818
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

Keywords

  • Chol-1 gangliosides
  • lectins
  • nerve regeneration
  • sialoadhesins

ASJC Scopus subject areas

  • General

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