Transport of surface mannose 6-phosphate receptor to the Golgi complex in cultured human cells.

The cation-independent mannose 6-phosphate receptor (MPRCI) functions in the packaging of both newly made and extracellular lysosomal enzymes into lysosomes. The subcellular location of MPRCI reflects these two functions; receptor is found in the Golgi complex, in endosomes, and on the cell surface. To learn about the intracellular pathway followed by surface receptor and to study the relationship between the receptor pools, we examined the entry of the surface MPRCI into Golgi compartments that contain sialyltransferase. Sialic acid was removed from surface-labeled K562 cultured human erythroleukemia cells by neuraminidase treatment. When the cells were returned to culture at 37 degrees C, surface MPRCI was resialylated by the cells with a half-time of 1-2 h. Resialylation was inhibited by reduced temperature, a treatment that allows surface molecules to reach endosomes but blocks further transport. These results indicate that surface MPRCI is transported to the sialyltransferase compartment in the Golgi complex. After culture at 37 degrees C, a small fraction (10-20%) of the resialylated receptor was found on the cell surface. Because a similar fraction of the total receptor pool is found on the cell surface, it is likely that cell surface MPRCI mixes with the cellular pool after resialylation. These data also support the idea that extracellular and newly made lysosomal enzymes are transported to lysosomes through a common compartment.