Phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases by human fibroblasts

Abstract

These authors recently presented data showing that mannose-6-phosphate was a potent competitive inhibitor of pinocytosis of human platelet β-glucuronidase, and that treatment of 'high-uptake' forms of the enzyme with alkaline phosphatase destroyed the high-uptake property of the enzymes without diminishing its catalytic activity. These data indicate that phosphate is a necessary component of the recognition marker on the enzyme for pinocytosis by human fibroblasts, and suggest that phosphate on high-uptake forms of the enzyme is present as a phosphohexosyl moiety. Results presented here show that mannose-6-phosphate is also a potent inhibitor of pinocytosis of the following enzyme preparations: β-glucuronidase from human spleen, liver, placenta, and urine; β-hexosaminidase and β-galactosidase from human platelets; β-hexosaminidase from human fibroblast secretions. Alkaline phosphatase treatment of all of these enzymes except β-galactosidase, which was unstable to the incubation conditions and could not be tested, greatly diminished the uptake activity of the enzymes without diminishing their catalytic activity. These results suggest that phosphohexosyl recognition is a general characteristic of pinocytosis of lysosomal glycosidases.