CLONING AND CHARACTERIZATION OF AN EXTRACELLULAR CA2+-SENSING RECEPTOR FROM BOVINE PARATHYROID
CLONING AND CHARACTERIZATION OF AN EXTRACELLULAR CA2+-SENSING RECEPTOR FROM BOVINE PARATHYROID
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DOI：
10.1038/366575a0
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发表时间：
1993-12-09
期刊：
影响因子：
64.8
通讯作者：
HEBERT, SC
中科院分区：
文献类型：
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作者：
BROWN, EM;GAMBA, G;HEBERT, SC
维持复杂生物体内稳定的内部环境需要专门的细胞来感知特定离子（如Ca 2+）的细胞外浓度的变化。虽然这种离子传感器的分子性质尚不清楚，但甲状旁腺细胞具有细胞表面Ca 2+感应机制，该机制也识别三价和多价阳离子（如新霉素），并通过改变磷酸肌醇周转率和胞质Ca 2+来调节甲状旁腺激素分泌1 -4。后者通过作用于肾脏和骨骼恢复正常钙血症2。我们现在报告的克隆互补DNA编码的细胞外钙离子敏感受体从牛甲状旁腺的药理学和功能特性几乎相同的天然受体。新的约120 K受体与代谢型谷氨酸受体5的相似性有限，并且具有较大的胞外结构域，含有可能参与钙结合的酸性氨基酸残基簇，与G蛋白偶联受体超家族中的7个跨膜结构域偶联。
MAINTENANCE of a stable internal environment within complex organisms requires specialized cells that sense changes in the extracellular concentration of specific ions (such as Ca2+). Although the molecular nature of such ion sensors is unknown, parathyroid cells possess a cell surface Ca2+-sensing mechanism that also recognizes trivalent and polyvalent cations (such as neomycin) and couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation of parathyroid hormone secretion1-4. The latter restores normocalcaemia by acting on kidney and bone2. We now report the cloning of complementary DNA encoding an extracellular Ca2+-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor. The novel approximately 120K receptor shares limited similarity with the metabotropic glutamate receptors5 and features a large extracellular domain, containing clusters of acidic amino-acid residues possibly involved in calcium binding, coupled to a seven-membrane-spanning domain like those in the G-protein-coupled receptor superfamily.