Gangliosides in cell recognition and membrane protein regulation

Gangliosides, sialic acid-bearing glycosphingolipids, are expressed on all vertebrate cells, and are the major glycans on nerve cells. They are anchored to the plasma membrane through their ceramide lipids with their varied glycans extending into the extracellular space. Through sugar-specific interactions with glycan-binding proteins on apposing cells, gangliosides function as receptors in cell-cell recognition, regulating natural killer cell cytotoxicity via Siglec-7, myelin-axon interactions via Siglec-4 (myelin-associated glycoprotein), and inflammation via E-selectin. Gangliosides also interact laterally in their own membranes, regulating the responsiveness of signaling proteins including the insulin, epidermal growth factor, and vascular endothelial growth factor receptors. In these ways, gangliosides act as regulatory elements in the immune system, in the nervous system, in metabolic regulation, and in cancer progression.