Procathepsins L and D are membrane-bound in acidic microsomal vesicles.
Procathepsins L and D, the proenzyme forms of two lysosomal proteases, are shown to bind to mouse fibroblast microsomal membranes at acidic pH. The propeptide of procathepsin L is necessary for membrane association because the mature forms of this lysosomal protein did not bind to the membranes. Both proenzymes were eluted from the membranes by increasing either the pH or the ionic strength of the buffer, so they are peripheral proteins that interact ionically with the membranes. The proenzymes were not eluted from the membranes with 50 mM mannose or 10 mM mannose 6-phosphate, which suggests that carbohydrate does not mediate membrane binding. Membrane binding is probably a specific, protein-mediated interaction since treatment of the microsomes with trypsin reduced by half the amount of procathepsin L which bound to the membranes, and binding of procathepsin L to the membranes was saturable. One or more "lysosomal proenzyme receptors" capable of binding to lysosomal proenzymes at acidic pH could complement the mannose 6-phosphate receptor system in prelysosomes and sort certain lysosomal proenzymes to lysosomes.
McIntyre
G F
GF
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill 27599.
Erickson
A H
AH
D000818:Animals; D002402:Cathepsin D / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D009994:Osmolar Concentration; D011233:Precipitin Tests
D004792:Enzyme Precursors; D008565:Membrane Proteins; D002403:Cathepsins; C063905:procathepsin L; D056668:Cathepsin L; C058345:procathepsin D; D002402:Cathepsin D