The following points highlight the two main processes which requires involvement of glycoproteins. The processes are: 1. Importance of Glycoproteins in Fertilization 2. Selectins Play Key Roles in Inflammation.
Process # 1. Importance of Glycoproteins in Fertilization:
(a) A sperm has to traverse the Zona Pellucida (ZP), a thick, transparent, non-cellular envelope that surrounds the oocyte to reach the plasma membrane of an oocyte.
(b) The Zona Pellucida contains three glycoproteins, ZPI-3.ZP3 is an O-linked glycoprotein that functions as a receptor for the sperm. A protein on the sperm surface, galactosyl transferase, interacts with oligosaccharide chains ofZP3. This interaction induces the acrosomal reaction in which enzymes (proteases and hyaluronidase) of the sperm are released and this helps the sperm to pass through the Zona Pellucida and reach the plasma membrane of the oocyte.
(c) Another glycoprotein, pH-30, is important in binding of the PM of the sperm of the oocyte and also in the fusion of the two membranes. These interactions enable the sperm to enter and thus fertilize the oocyte.
(d) It is also possible to inhibit fertilization by developing drugs or antibodies that interfere with the normal functions of ZP3 and PH-30 and thus act as contraceptive agents.
Process # 2. Selectins Play Key Roles in Inflammation:
(a) Leukocytes have important roles in many inflammatory and immunologic phenomena. Leukocytes and endothelial cells contain specific lectins, called selectins, on their surfaces.
(b) Selectins are single-chain Ca2+-binding trans-membrane proteins that contain a number of domains. Their amino terminal-ends contain the lectin domain which is involved in binding to specific carbohydrate ligands.
(c) The adhesion of neutrophils to endothelial cells of post-capillary venules occurs in several stages. The initial baseline stage occurs by slowing or rolling of the neutrophils being mediated by selectins. During this stage, activation of the neutrophils by various chemical mediators occurs resulting in a change of shape of the neutrophils and firm adhesion of these cells to the endothelium.
An additional set of adhesion molecules is involved in firm adhesion, namely, LFA-1 and Mac-1 on the neutrophils and ICAM- 1 and ICAM-2 on endothelial cells.
(d) The selectins bind sialylated and fucosylated oligosaccharides, and in particular all bind sialy-Lewis, a structure present on both glycoproteins and glycolipids. Sulfatides may be ligands in certain instances.
It is tried to synthesize compounds that block selectin-ligand interactions and thus may inhibit the inflammatory response, (e) Cancer cells exhibit sialyl-Lewis and other selectin ligands on their surfaces. These ligands play a role in the invasion and metastasis of cancer cells.