Effect of wortmannin on M AN-6-P/IGF-U receptor trafficking

The effect of wortmannin on the trafficking of the Man-6-P/IGF-II receptor (MPR) and its ligand β-glucuronidase has been determined in murine L cells, BW 5147 lymphoma cells and NRK cells. The drug induced a 90% decrease in the steady-state level of the MPR at the plasma membrane without affecting the rate of internalization, indicating that the return of receptor from endosomes to the plasma membrane is retarded. Wortmannin also slowed movement of the MPR from endosomes to the trans-Golgi network by about 50% as determined by a resialylation assay. The marked retention of the MPR in endosomes helps to explain the hypersecretion of procathepsin D which is induced by wortmannin. In addition, the drug slowed delivery of endocytosed β-glucuronidase from endosomes to dense lysosomes. These data, taken together with the published reports of others, indicate that wortmannin inhibits membrane trafficking out of multiple compartments of the endosomal system.