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Lysosomal enzymes containing one or two mannose 6-phosphate (man6P) moieties are moved about in the cell by two distinct but interconnected cycles by means of 300 kDa cation independent mannose 6-phospate receptors (CI-MPR). The biosynthetic cycle refers to the MPR transport of newly synthesized lysosomal enzymes from the trans Golgi network to late endosomes or early lysosomes. The endocytic cycle transports extracellular lysosomal enzymes from the plasma membrane via clathrin-coated vesicles to early endosomes. The entire pool of MPRs cycles between these cellular compartments every 3 hours. The steady state distribution of MPR's is predominantly within late endosomes, fewer in the trans Golgi network and ~10 % at cell surface. In addition to its man6P binding activity, the MPR contains a separate binding site for the type II insulin-like growth factor and is capable of binding both man6P and IGF-II simultaneously. An ~240 kDa soluble, truncated form, representing the extracellular domain of the protein, has also been found circulating in serum and is capable of binding both ligands.
