THE LYSOSOMAL PROENZYME RECEPTOR THAT BINDS PROCATHEPSIN-L TO MICROSOMAL-MEMBRANES AT PH 5 IS A 43-KDA INTEGRAL MEMBRANE-PROTEIN

Two lysosomal proenzymes, procathepsins L and D, bind to mouse fibrobl ast microsomal membranes at acidic pH. This membrane association is in dependent of the mannose-6-phosphate receptors and requires the presen ce of the N-terminal propeptides of the enzymes. We have identified th e protein that specifically binds procathepsin L at pH 5. A 43-kDa mem brane protein coimmunoprecipitated with procathepsin L at pH 5 but not at pH 7 when cells were denatured with detergents. Similarly, a 43-kD a integral membrane protein bound procathepsin L in three kinds of lig and blots at pH 5 but not at pH 7. A synthetic peptide containing the 24 N-terminal residues of mouse procathepsin L blocked the binding of procathepsin L to this integral membrane protein on ligand blots. Thes e results indicate that the 43-kDa integral membrane protein is a lyso somal proenzyme receptor that specifically binds the procathepsin L ac tivation peptide at acidic pH.