More than 25 distinct receptors are known to participate in receptor-mediated endocytosis of different types of molecules. They all apparently use clathrin-dependent internalization routes and are guided into clathrin-coated pits by signals in their cytoplasmic tails that bind to adaptor proteins in the clathrin coat. Many of these receptors, like the LDL receptor, enter coated pits irrespective of whether they have bound their specific ligands. Others enter preferentially when bound to a specific ligand, suggesting that a ligand-induced conformational change is required for them to activate the signal sequence that guides them into the pits. Since most plasma membrane proteins fail to become concentrated in clathrin-coated pits, the pits serve as molecular filters, preferentially collecting certain plasma membrane proteins (receptors) over others.
Electron-microscope studies of cultured cells exposed simultaneously to different labeled ligands demonstrate that many kinds of receptors can cluster in the same coated pit, whereas some other receptors cluster in different clathrin-coated pits. The plasma membrane of one clathrin-coated pit can accommodate more than 100 receptors of assorted varieties.
specific proteins are retrieved from early endosomes and returned to the plasma Membrane
Early endosomes are the main sorting station in the endocytic pathway, just as the cis and trans Golgi networks serve this function in the secretory pathway. In the mildly acidic environment of the early endosome, many internalized receptor proteins change their conformation and release their ligand, as already discussed for the M6P receptors. Those endocytosed ligands that dissociate from their receptors in the early endosome are usually doomed to destruction in lysosomes (although cholesterol is an exception, as just discussed), along with the other soluble contents of the endosome. Some other endocytosed ligands, however, remain bound to their receptors, and thereby share the fate of the receptors.
In the early endosome, the LDL receptor dissociates from its ligand, LDL, and is recycled back to the plasma membrane for reuse, leaving the discharged LDL to be carried to lysosomes (Figure 13–52). The recycling transport vesicles bud from long, narrow tubules that extend from the early endosomes. It is likely that the geometry of these tubules helps the sorting process: because tubules have a large membrane area enclosing a small volume, membrane proteins become enriched over soluble proteins. The transport vesicles return the LDL receptor directly to the plasma membrane.
The transferrin receptor follows a similar recycling pathway as the LDL receptor, but unlike the LDL receptor it also recycles its ligand. Transferrin is a soluble
Figure 13–52 The receptor-mediated endocytosis of LDL. note that the ldl dissociates from its receptors in the acidic environment of the early endosome. after a number of steps, the ldl ends up in endolysosomes and lysosomes, where it is degraded to release free cholesterol. In contrast, the ldl receptors are returned to the plasma membrane via transport vesicles that bud off from the tubular region of the early endosome, as shown. for simplicity, only one ldl receptor is shown entering the cell and returning to the plasma membrane. whether it is occupied or not, an ldl receptor typically makes one round trip into the cell and back to the plasma membrane every 10 minutes, making a total of several hundred trips in its 20-hour life-span.