Membrane proteins in cells are continually replaced as old proteins are removed and new ones are synthesized. One way these proteins are marked for replacement is by attaching ubiquitin to the cytoplasmic portion of the protein. Ubiquitin, a 76-amino acid protein, is covalently attached to the membrane protein, usually lysine, by a group of enzymes called ubiquitin protein ligases. The Nedd4/Nedd4-like family is an important group of these ligases. Once a membrane protein is ubiquitinated, it undergoes endocytosis and is degraded by lysosomes or the proteasome. Deubiquitinating enzymes (DUBs) are also present in cells. The duration a protein remains in the plasma membrane depends on the rate at which ubiquitin groups are added by ligases compared to the rate at which they are removed by DUBs. For instance, aldosterone, an adrenal hormone, inhibits Nedd4-2, thus preventing ubiquitination of ENaC in the apical membrane of epithelial cells. This leads to a longer retention of channels in the membrane, allowing more Na+ to enter the cell and be reabsorbed. Macrophages have receptors on their surface that bind to the Fc portion of immunoglobulins. When bacteria enter the body, they are often coated with antibodies through a process called opsonization. These bacteria then attach to macrophage membranes via the fragment crystallizable (Fc) portion of the immunoglobulin, undergo phagocytosis, and get destroyed inside the cell. Receptor-mediated endocytosis is another mechanism of endocytosis that enables the uptake of specific molecules into the cell. In this type of endocytosis, molecules bind to receptors on the cell surface. Accessory proteins like adaptin, clathrin, and the GTPase dynamin are involved in endocytosis.
Proteins within the plasma membrane of cells are constantly being removed and replaced with newly synthesized proteins. As a result, membrane proteins are constantly being replaced. One mechanism by which membrane proteins are “tagged” for replacement is by the attachment of ubiquitin to the cytoplasmic portion of the protein. Ubiquitin is a 76–amino acid protein that is covalently attached to the membrane protein (usually to lysine) by a class of enzymes called ubiquitin protein ligases. One important group of these ligases is the developmentally downregulated protein 4 (Nedd4)/Nedd4-like family. Once a membrane protein is ubiquitinated, it undergoes endocytosis and is degraded either by lysosomes or by the proteosome. Cells also contain deubiquitinating enzymes (DUBs). Thus the amount of time a protein stays in the plasma membrane depends on the rate that ubiquitin groups are added by the ligases versus the rate that they are removed by the DUBs. For example, Na+ reabsorption by the collecting ducts of the kidneys is stimulated by the adrenal hormone aldosterone (see ). One of the actions of aldosterone is to inhibit Nedd4-2. This prevents ubiquitination of ENaC in the apical membrane of epithelial cells. Thus the channels are retained for a longer period of time in the membrane, and as a result, more Na+ enters the cell and is thereby reabsorbed.
macrophages have receptors on their surface that bind the Fc portion of immunoglobulins. When bacteria invade the body they are often coated with antibody, a process called opsonization. These bacteria then attach to the membrane of macrophages via the fragment crystallizable (Fc) portion of the immunoglobulin, undergo phagocytosis, and are destroyed inside the cell. The third mechanism of endocytosis is receptor-mediated endocytosis, which allows the uptake of specific molecules into the cell. In this form of endocytosis, molecules bind to receptors on the surface of the cell. Endocytosis involves a number of accessory proteins, including adaptin, clathrin, and the GTPase dynamin (
Fig. 1.5