Secretion of human meprin from intestinal epithelial cells depends on differential expression of the α and β subunits

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Abstract
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 α and β subunits. In transfected cells, intracellular proteolytic removal of the membrane anchor from the α subunit results in its secretion, while the β subunit and α/β heterodimers are retained at the cell membrane. We investigated the consequence of differential intracellular processing of α and β subunits in the human small and large intestine using subunit-specific immunohistochemistry, in situ hybridization and biosynthetic studies in organ culture. In the ileum, both subunits localize to the brush-border membrane of villus enterocytes. In contrast, the β subunit is not expressed in the colon, which leads to the secretion of the α subunit. We conclude that differential expression of meprin α and β subunits is a unique means of targeting the proteolytic activity of the α 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 α and β subunits are also coexpressed in distinct lamina propria leukocytes, suggesting an additional role for this protease in leukocyte function in the intestinal mucosa.

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