Human DNase I Contains Mannose 6-Phosphate and Binds the Cation-Independent Mannose 6-Phosphate Receptor

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Abstract
DNase I isolated from human urine (hDNase) or expressed in Chinese hamster ovary (CHO) cells contains mannose-phosphorylated oligosaccharides. hDNase binds to a column of immobilized cation-independent mannose 6-phosphate receptor, with the strongest binding exhibited by the protein bearing diphosphorylated oligosaccharides. The binding is inhibited by 5 mM mannose 6-phosphate, and can be prevented by prior treatment of hDNase with alkaline phosphatase. Phosphorylated high-mannose oligosaccharides were observed at both sites of glycosylation in hDNase by high-performance liquid chromatography-mass spectrometry of a tryptic digest These results indicate that hDNase, though not an acid hydrolase, may enter the lysosomal trafficking pathway, and may have evolved from a lysosomal enzyme.