Secretion of human meprin from intestinal epithelial cells depends on differential expression of the α and β subunits
Secretion of human meprin from intestinal epithelial cells depends on differential expression of the α and β subunits
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DOI：
10.1046/j.1432-1327.1999.00071.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Sterchi, EE
中科院分区：
文献类型：
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作者：
Lottaz, D;Hahn, D;Sterchi, EE
人meprin（N-苯甲酰基-L-酪氨酰-对氨基苯甲酸水解酶，EC 3.4.24.18）是一种astacin型金属蛋白酶，由肠上皮细胞表达为α和β亚基的二聚体蛋白复合物。在转染的细胞中，细胞内蛋白水解从α亚基去除膜锚导致其分泌，而β亚基和α/β异二聚体保留在细胞膜上。我们调查的后果，差异细胞内加工的α和β亚基在人类小肠和大肠亚基特异性免疫组织化学，原位杂交和生物合成研究在器官培养。在回肠中，两个亚基定位于绒毛肠上皮细胞的刷状缘膜。相反，β亚基在结肠中不表达，这导致α亚基的分泌。我们的结论是，差异表达的meprin α和β亚基是一种独特的手段，针对的α亚基的蛋白水解活性，无论是在回肠刷状缘膜或在结肠腔，这表明细胞相关的和管腔meprin的双重功能。甲氨蝶呤α和β亚基也在不同的固有层白细胞中共表达，表明这种蛋白酶在肠粘膜白细胞功能中的额外作用。
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 transfected cells, intracellular proteolytic removal of the membrane anchor from the alpha subunit results in its secretion, while the beta subunit and alpha/beta heterodimers are retained at the cell membrane. We investigated the consequence of differential intracellular processing of alpha and beta 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 beta subunit is not expressed in the colon, which leads to the secretion of the alpha subunit. We conclude that differential expression of meprin alpha and beta subunits is a unique means of targeting 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 subunits are also coexpressed in distinct lamina propria leukocytes, suggesting an additional role for this protease in leukocyte function in the intestinal mucosa.