Abstract
Lysosomal proteins are synthesized at the rough ER and initially follow the secretory pathway. En route to the Golgi, mannose 6-phosphate residues (M6P) are attached to N-linked oligosaccharides of soluble lysosomal proteins and serve as a sorting signal. In the Golgi, lysosomal proteins are separated from the secretory pathway by binding to mannose 6-phosphate receptors (MPR). The receptor-ligand complexes are delivered via clathrin-coated vesicles to an acidified prelysosomal compartment, where due to a low pH the MPR-ligand complexes dissociate. Lysosomal proteins are subsequently sorted into dense lysosomes, while the receptors return to the Golgi or the plasma membrane and are available for further rounds of transport. Extracellular ligands can be internalized by MPR located at the plasma membrane. Two types of MPR of molecular sizes of 300 and 46kDa are known. While the two receptors show similar binding properties for M6P-ligands, most of the intracellular sorting is accomplished by the MPR 300. Furthermore, only the MPR 300 endocytoses extracellular ligands from the cell surface and this type of receptor contains, in many species, an additional binding site for the insulin-like growth factor II (IGF II)
