Nonlysosomal processing of cell-surface heparan sulfate proteoglycans. Studies of I-cells and NH4Cl-treated normal cells

The metabolism of cell-associated proteoglycans, labeled in the glycosaminoglycan portion with 35SO2-4, was studied in normal skin fibroblasts (SL66 cells), NH4Cl-treated SL66 fibroblasts, and in I-cells derived from patients with mucolipidosis II. Kinetic data from label-chase experiments and gel filtration analysis of the molecular weight distribution of the radiolabeled glycosaminoglycans indicated that I-cells and NH4Cl-treated normal fibroblasts (a) internalize cell surface proteoglycans, (b) remove glycosaminoglycan chains from proteoglycan core proteins, and (c) degrade heparan sulfate glycosaminoglycan chains via an endoglycosidic activity. These processes occur with rates comparable to those in normal fibroblasts. The data are consistent with the hypothesis that the glycosaminoglycan chains of cell-surface proteoglycans are separated from the protein cores in a nonlysosomal compartment prior to the transport of these chains to lysosomes for degradation. These observations also raise the possibility that this early step in separation of glycosaminoglycan chains from protein cores may serve to regulate the levels of glycosaminoglycan-free core protein observed in various cells.