Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling.
Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling.
复制标题
NOS1AP 对 NMDA 受体-nNOS 信号传导的作用机制。
DOI：
10.3389/fncel.2014.00252
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发表时间：
2014
影响因子：
5.3
通讯作者：
Lai YY
中科院分区：
文献类型：
--
作者：
Courtney MJ;Li LL;Lai YY
NMDA受体（NMDAR）是谷氨酸门控钙通道，在神经元功能的基本方面发挥关键作用。受体功能失调导致许多疾病。NMDAR通过PSD 95募集钙依赖性酶nNOS被视为神经元功能障碍的关键因素。nNOS衔接蛋白（NOS 1AP）最初被描述为PSD 95：nNOS相互作用的竞争者，被认为是NMDAR驱动的nNOS功能的抑制剂。在NMDAR过度活跃的情况下，如兴奋性毒性，人们期望NOS 1AP具有神经保护作用。NMDAR活性低下的情况，被认为发生在精神分裂症中，可能会被NOS 1AP加重。事实上，GWAS已经将NOS 1AP和nNOS与精神分裂症联系起来。一些研究表明，NOS 1AP可以介导而不是抑制NMDAR/nNOS依赖性反应，包括兴奋性毒性信号。然而，NOS 1AP作为nNOS抑制剂的概念在人类疾病遗传学研究中占主导地位。在这里，我们回顾了实验证据，以评估这一明显的争议，考虑是否已知的功能NOS 1AP可能会保护神经元对NMDAR失调，并强调未来的调查，以阐明这种衔接蛋白的功能的特定领域。
NMDA receptors (NMDAR) are glutamate-gated calcium channels that play pivotal roles in fundamental aspects of neuronal function. Dysregulated receptor function contributes to many disorders. Recruitment by NMDARs of calcium-dependent enzyme nNOS via PSD95 is seen as a key contributor to neuronal dysfunction. nNOS adaptor protein (NOS1AP), originally described as a competitor of PSD95:nNOS interaction, is regarded an inhibitor of NMDAR-driven nNOS function. In conditions of NMDAR hyperactivity such as excitotoxicity, one expects NOS1AP to be neuroprotective. Conditions of NMDAR hypoactivity, as thought to occur in schizophrenia, might be exacerbated by NOS1AP. Indeed GWAS have implicated NOS1AP and nNOS in schizophrenia. Several studies now indicate NOS1AP can mediate rather than inhibit NMDAR/nNOS-dependent responses, including excitotoxic signaling. Yet the concept of NOS1AP as an inhibitor of nNOS predominates in studies of human disease genetics. Here we review the experimental evidence to evaluate this apparent controversy, consider whether the known functions of NOS1AP might defend neurons against NMDAR dysregulation and highlight specific areas for future investigation to shed light on the functions of this adaptor protein.
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影响因子：
7.3
作者：
Florio, S. K.;Loh, C.;Lai, Y.
通讯作者：
Lai, Y.
影响因子：
4.7
作者：
COURTNEY, MJ;NICHOLLS, DG
通讯作者：
NICHOLLS, DG
影响因子：
5.3
作者：
Citrome, Leslie
通讯作者：
Citrome, Leslie
影响因子：
7.8
作者：
Ghatan, S;Larner, S;Kinoshita, Y;Hetman, M;Patel, L;Xia, Z;Youle, R J;Morrison, R S
通讯作者：
Morrison, R S
影响因子：
--
作者：
Delorme R;Betancur C;Scheid I;Anckarsäter H;Chaste P;Jamain S;Schuroff F;Nygren G;Herbrecht E;Dumaine A;Mouren MC;Råstam M;Leboyer M;Gillberg C;Bourgeron T
通讯作者：
Bourgeron T