In vitro activation of neuraminidase in the beta-galactosidase-neuraminidase-protective protein complex by cathepsin C.
Neuraminidase can be activated by incubation of crude glycoprotein fractions at acidic pH for 90 minutes at physiological temperature. This activation is inhibited by leupeptin. Incubation of the purified neuraminidase-beta-galactosidase-protective protein complex under the same conditions used for crude glycoprotein fractions did not lead to enhanced neuraminidase activity, but incubation in the presence of exogenous Cathepsin C at 4 degrees C resulted in marked enhancement of neuraminidase activity. This activation was again inhibited by leupeptin. Cathepsin D treatment resulted in destruction of neuraminidase under the same conditions and this effect was again inhibited by leupeptin. beta-galactosidase in crude glycoprotein fractions and in the complex was resistant to both Cathepsin C and D, while homogeneous beta-galactosidase was inactivated by these enzymes. We suggest that in vitro activation of neuraminidase may mimic the in vivo intralysosomal conversion of the neuraminidase precursor into the mature form of the enzyme.
D'Agrosa
R M
RM
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Callahan
J W
JW
D020789:Cathepsin C; D002402:Cathepsin D / Q000494:pharmacology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D005696:Galactosidases / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D009439:Neuraminidase / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D001616:beta-Galactosidase / Q000378:metabolism*
D004792:Enzyme Precursors; D006023:Glycoproteins; D046911:Macromolecular Substances; D005696:Galactosidases; D009439:Neuraminidase; D001616:beta-Galactosidase; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D020789:Cathepsin C; D002402:Cathepsin D