Posttranslational processing of secretory component in the rat jejunum by a brush border metalloprotease.
Secretory component (SC) is a glycoprotein that mediates the transcellular transport of polymeric immunoglobulins into external secretions. SC is synthesized and inserted into the plasma membrane of epithelial cells and hepatocytes as a transmembrane protein, where it serves as a receptor for polymeric immunoglobulins. SC is posttranslationally cleaved to a soluble protein before secretion into external fluids. In the rat jejunum, we observed that the molecular weights of both the major membrane and soluble forms of SC were 10,000-20,000 smaller than the comparable hepatic forms of the glycoprotein. We therefore set out to determine the reason for the differences in size of SC between these two tissues. The smaller size of jejunal SC was not due to the action of pancreatic proteases or differential glycosylation but was due to proteolysis by a jejunal brush border protease. The protease was characterized as a metalloprotease, with a pH optimum of approximately 5. It is present in jejunal, ileal, and renal tubular brush borders as an integral membrane constituent. When the protease was inhibited in vivo, conversion of jejunal secretory component to the smaller size was partially prevented. Thus, in the rat jejunum, SC undergoes two posttranslational proteolytic events: conversion of membrane secretory component to the soluble form and conversion of soluble SC to a smaller size by a previously undescribed brush border protease.
D000818:Animals; D001646:Bile / Q000032:analysis; D002241:Carbohydrates / Q000032:analysis; D003106:Colon / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007128:Immunoglobulin Fragments / Q000096:biosynthesis*; D007163:Immunosorbent Techniques; D007583:Jejunum / Q000201:enzymology / Q000648:ultrastructure*; D008297:Male; D008666:Metalloendopeptidases; D008871:Microvilli / Q000201:enzymology; D008892:Milk / Q000032:analysis; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains; D012635:Secretory Component / Q000096:biosynthesis*
D002241:Carbohydrates; D007128:Immunoglobulin Fragments; D012635:Secretory Component; D010450:Endopeptidases; D008666:Metalloendopeptidases