Secretion of human meprin from intestinal epithelial cells depends on differential expression of the alpha and beta subunits

Human meprin (N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase, EC 3.4.24. 18), an astacin-type metalloprotease, is expressed by intestinal epithelial cells as a dimeric protein complex of alpha and beta subunits, In transfec ted cells, intracellular proteolytic removal of the membrane anchor from th e alpha subunit results in its secretion, while the beta subunit and alpha/ beta heterodimers are retained at the cell membrane. We investigated the co nsequence of differential intracellular processing of alpha and beta subuni ts in the human small and large intestine using subunit-specific immunohist ochemistry, in situ hybridization and biosynthetic studies in organ culture . In the ileum, both subunits localize to the brush-border membrane of vill us enterocytes. In contrast, the beta subunit is not expressed in the colon , which leads to the secretion of the alpha subunit. We conclude that diffe rential expression of meprin alpha and beta subunits is a unique means of t argeting the proteolytic activity of the alpha subunit either to the brush- border membrane in the ileum or to the lumen in the colon, suggesting dual functions of cell-associated and luminal meprin. Meprin alpha and beta subu nits are also coexpressed in distinct lamina propria leukocytes, suggesting an additional role for this protease in leukocyte function in the intestin al mucosa.