Platelet Plasma Membrane Glycoproteins in Normal and Genetically Abnormal Platelets

One approach to determine what specialized structures on the platelet membrane surface perform platelet specific functions is to compare the surface of normal to genetically abnormal platelets. We have used three techniques; lactoperoxidase-catalyzed iodination, neuraminidase/galactose oxidase/(³H)-NaBH₄ labeling, and periodate/(³H)-NaBH₄ labeling, to investigate the molecular organization of the proteins in these membranes. Several generalizations can be made about the normal membrane: (i) all of the major proteins exposed on the surface (12 have been identified thus far), are glycosylated, (ii) some of these glycoproteins are trans-membrane (i.e., they span the thickness of the membrane), (iii) the glycosylated segments are exposed to the outside of the cell, (iv) many disulfides (both inter- and intramolecular) are present in the platelet membrane glycoproteins, and (v) most of these glycoproteins contain sialic acid.

Analysis of the glycoprotein composition of the platelets from 16 individuals with Glanzmann’s thrombasthenia (characterized by a lack of aggregation) showed a decreased concentration of glycoproteins IIb and III. In contrast, platelets from an individual with Bernard-Soulier syndrome (characterized by absent adhesion) had primarily a decrease in glycoprotein Ib. The data demonstrate that both genetic abnormalities are caused by different defects in platelet membrane glycoproteins and suggest molecular entities which may be involved in specific platelet functions. Supported by NIH Career Development Award HL-0080 and Grant HL-15616.