Bases moléculaires du transport vers les lysosomes

Abstract

In high eucaryotes, the mannose 6-phosphate receptors (MPRs) are essential components that allow proper targeting of lysosomal enzymes to lysosomes. Two mannose 6-phosphate receptors have been characterized. The first has a dual function. It binds the phosphorylated oligosaccharides of the lysosomal enzymes and the insulin-like growth factor II, a non-glycosylated polypeptide. The second only binds lysosomal enzymes. It is still unclear why mammalian cells need two different MPRs that apparently show similar targeting functions. The MPRs are found in several intracellular compartments. They form however one functional pool of receptors. They recycle between the transGolgi network and the endocytic compartments to divert the newly synthesized lysosomal enzymes from the secretory pathway. They also recycle between the plasma membrane and the endosomes for internalization of extracellular ligands. At steady state, the MPRs are mostly localized to endosomes where ligands dissociate before being transported to the lysosomes. These steps of transport, some of which involving the formation of clathrin-coated vesicles require signals contained in their cytoplasmic domains. These latter interact with cytosolic components which allow the segregation and clustering of the MPRs into transport vesicles.