Myelin-associated glycoprotein binding to gangliosides. Structural specificity and functional implications.
Myelin-associated glycoprotein (MAG), which mediates certain myelin-neuron cell-cell interactions, is a lectin that binds to sialylated glycoconjugates. Gangliosides, the most abundant sialylated glycoconjugates in the brain, may be the functional neuronal ligands for MAG. Cells engineered to express MAG on their surface adhered specifically to gangliosides bearing an alpha 2,3-linked N-acetylneuraminic acid on a terminal galactose, with the following relative potency: GQ1b alpha >> GD1a, GT1b >> GM3, GM4 (GM1, GD1b, GD3, and GQ1b did not support adhesion). MAG binding was abrogated by modification of the carboxylic acid, any hydroxyl, or the N-acetyl group of the ganglioside's N-acetylneuraminic acid moiety. Related immunoglobulin (Ig) superfamily members either failed to bind gangliosides (CD22) or bound with less stringent specificity (sialoadhesin), whereas a modified form of MAG (bearing three of its five extra-cellular Ig-like domains) bound only GQ1b alpha. Enzymatic removal of sialic acids from the surface of intact nerve cells altered their functional interaction with myelin. These data are consistent with a role for gangliosides in MAG-neuron interactions.
Schnaar
R L
RL
Department of Pharmacology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Collins
B E
BE
Wright
L P
LP
Kiso
M
M
Tropak
M B
MB
Roder
J C
JC
Crocker
P R
PR
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D005732:Gangliosides / Q000737:chemistry* / Q000378:metabolism*; D006017:Glycolipids / Q000737:chemistry; D006801:Humans; D008322:Mammals; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry* / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1; D013329:Structure-Activity Relationship
D005732:Gangliosides; D006017:Glycolipids; D008562:Membrane Glycoproteins; D018992:Myelin-Associated Glycoprotein; D009844:Oligosaccharides; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1