MEMBRANE GLYCOLIPIDS AND THEIR RELATIONSHIP TO THE STRUCTURE AND FUNCTION OF CELL SURFACE RECEPTORS FOR GLYCOPROTEIN HORMONES, BACTERIAL TOXINS, AND INTERFERON

Abstract

Gangliosides inhibit 125 I-thyrotropin (TSH) binding to the thyrotropin receptor. This inhibition, which appears to be hormonally specific, is critically altered by the number and location of the sialic acid residues within the ganglioside structure. The inhibition results from the interaction of gangliosides with TSH, rather than with the membrane receptor. The ganglioside-TSH interaction is associated with a distinct conformational change of the TSH molecule. The possibility that a ganglioside or ganglioside-like structure is a component of the thyrotropin receptor is suggested by the finding that gangliosides more complex than G M3 are present in bovine thyroid membranes in much higher quantities than have been previously found in extraneural tissue and are absent in a thyroid tumor with no TSH receptor activity. The finding that the B protein of cholera toxin, which also interacts with gangliosides, has a peptide sequence in common with the β sub-unit of TSH, suggests that TSH and cholera toxin may be analogous in their mode of action. It is suggested, therefore, that a ganglioside or ganglioside-like structure is a basic component of the thyrotopin receptor and that cholera toxin and TSH have a common mechanism by which their message is transmitted to the cell machinery.