Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity
Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity
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DOI：
10.1126/science.282.5392.1321
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发表时间：
1998-11-13
期刊：
影响因子：
56.9
通讯作者：
Sanes, JR
中科院分区：
文献类型：
--
作者：
Feng, GP;Tintrup, H;Sanes, JR
甘氨酸受体被一种细胞质蛋白Gen锚定在抑制性化学突触上。分子克隆揭示了地卟啉与原核生物和无脊椎动物蛋白质的相似性，这些蛋白质是合成钼酶活性所需的辅因子所必需的。小鼠的基因打靶实验表明，无论是脊髓甘氨酸受体的突触聚集，还是非神经组织中钼酶的活性，都需要吉普林。突变的表型类似于遗传性钼辅助因子缺乏和亢进(抑制性神经传递失败)的人类，这表明在这两种疾病中，Gen的功能可能受到损害。
Glycine receptors are anchored at inhibitory chemical synapses by a cytoplasmic protein, gephyrin. Molecular cloning revealed the similarity of gephyrin to prokaryotic and invertebrate proteins essential for synthesizing a cofactor required for activity of molybdoenzymes. Gene targeting in mice showed that gephyrin is required both for synaptic clustering of glycine receptors in spinal cord and for molybdoenzyme activity in nonneural tissues. The mutant phenotype resembled that of humans with hereditary molybdenum cofactor deficiency and hyperekplexia (a failure of inhibitory neurotransmission), suggesting that gephyrin function may be impaired in both diseases.