September 2010

Gangliosides as Mediators

Besides making lateral associations, gangliosides “shake hands” with complementary glycan-binding proteins (lectins) on adjacent cells to mediate cell-cell recognition. The disialoganglioside GD3 (Sia-Sia-Gal-Glc-Cer) engages a lectin on natural killer cells (Siglec-7) to suppress NK-mediated cytotoxicity. High-resolution X-ray crystallography of Siglec-7 bound to GD3 reveals an extended network of hydrogen bonds that, along with charge and hydrophobic interactions, defines the distinct glycan binding specificity and affinity of Siglec-7. Another member of the Siglec family, Siglec-4 (myelin-associated glycoprotein), is expressed on myelin and binds to gangliosides GD1a and GT1b on axons to stabilize them and regulate axon regeneration. The leukocyte adhesion lectin E-selectin, which initiates inflammation, binds to low-abundance gangliosides with very long glycan chains on human neutrophils, including gangliosides that have a 14-sugar linear chain terminated with sialic acid and carry multiple pendant fucose residues. These examples reveal that the diversity of ganglioside glycans (there are hundreds) support a variety of cell-cell recognition roles.

By their associations with each other, with signaling molecules in their own membranes and with lectins on apposing membranes, the gregarious gangliosides are lipids that grease the wheels of cellular communication.

Further Reading

Lopez, P. H., and Schnaar, R. L. (2009) Gangliosides in Cell Recognition and Membrane Protein Regulation. Curr. Opin. Struct. Biol. 19, 549-557.

Ronald L. Schnaar (schnaar@jhu.edu) is a professor in the department of pharmacology and molecular sciences and the department of neuroscience at the Johns Hopkins University School of Medicine.

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COMMENTS:

Very nice clearly written synopsis on the complexity of ganglioside interactions. Baiba Gillard Baylor College of Medicine

 

I will use this reference to excite my students about being introduced to the structures of and metabolism of gangliosides. -Kent Littleton

 

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