Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains
Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha 1-syntrophin mediated by PDZ domains
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DOI：
10.1016/s0092-8674(00)81053-3
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发表时间：
1996-03-08
期刊：
影响因子：
64.5
通讯作者：
Bredt, DS
中科院分区：
文献类型：
--
作者：
Brenman, JE;Chao, DS;Bredt, DS
神经元型一氧化氮合酶（nNOS）主要集中在脑的突触连接处和骨骼肌的运动终板。在这里，我们表明，N-末端的nNOS，其中包含一个PDZ蛋白基序，与类似的基序在突触后密度-95蛋白（PSD-95）和相关的新蛋白，PSD-93相互作用。nNOS和PSD-95在许多神经元群体中共表达，并且在小脑中存在PSD-95/nNOS复合物。PDZ结构域相互作用还介导nNOS与骨骼肌突触营养蛋白（一种肌营养不良蛋白相关蛋白）的结合。在nNOS（Delta/Delta）突变小鼠中鉴定的缺乏PDZ结构域的nNOS同种型不与脑中的PSD-95或骨骼肌肌膜相关。因此，含PDZ结构域的相互作用介导nNOS的突触结合，并且可能在大分子信号复合物的形成中发挥更普遍的作用。
Neuronal nitric oxide synthase (nNOS) is concentrated at synaptic junctions in brain and motor endplates in skeletal muscle. Here, we show that the N-terminus of nNOS, which contains a PDZ protein motif, interacts with similar motifs in postsynaptic density-95 protein (PSD-95) and a related novel protein, PSD-93. nNOS and PSD-95 are coexpressed in numerous neuronal populations, and a PSD-95/nNOS complex occurs in cerebellum. PDZ domain interactions also mediate binding of nNOS to skeletal muscle syntrophin, a dystrophin-associated protein. nNOS isoforms lacking a PDZ domain, identified in nNOS(Delta/Delta) mutant mice, do not associate with PSD-95 in brain or with skeletal muscle sarcolemma. Interaction of PDZ-containing domains therefore mediates synaptic association of nNOS and may play a more general role in formation of macromolecular signaling complexes.