Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses.
Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses.
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DOI：
10.1016/j.neuron.2014.10.010
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发表时间：
2014-10-22
期刊：
影响因子：
16.2
通讯作者：
Penzes, Peter
中科院分区：
文献类型：
--
作者：
Smith, Katharine R.;Kopeikina, Katherine J.;Fawcett-Patel, Jessica M.;Leaderbrand, Katherine;Gao, Ruoqi;Schuermann, Britta;Myczek, Kristoffer;Radulovic, Jelena;Swanson, Geoffrey T.;Penzes, Peter
最近的证据表明，谷氨酸能突触是精神疾病的关键致病部位。编码Ankyrin-G的ANK3基因常见和罕见的变异与双相情感障碍、精神分裂症和自闭症有关。在这里，我们证明了Ankyrin-G在AMPAR介导的突触传递和维持脊柱形态方面是不可或缺的。使用超分辨显微镜，我们发现Ankyrin-G在脊柱、头部和颈部形成了不同的纳米结构。在这些部位，它调节蘑菇状脊柱的结构和功能，很可能是作为突触周围的支架和脊柱颈部的屏障。神经元活动促进Ankyrin-G在不同的脊椎亚区积聚，在那里它对NMDA受体依赖的可塑性进行不同的调节。这些数据暗示，包含主要精神疾病风险分子ankyrin-G的突触下纳米结构域具有特定位置的功能，并为精神疾病风险分子的基础和翻译研究开辟了方向。
Recent evidence implicates glutamatergic synapses as key pathogenic sites in psychiatric disorders. Common and rare variants in the ANK3 gene, encoding ankyrin-G, have been associated with bipolar disorder, schizophrenia, and autism. Here we demonstrate that ankyrin-G is integral to AMPAR-mediated synaptic transmission and maintenance of spine morphology. Using super-resolution microscopy we find that ankyrin-G forms distinct nanodomain structures within the spine head and neck. At these sites, it modulates mushroom spine structure and function, likely as a perisynaptic scaffold and barrier within the spine neck. Neuronal activity promotes ankyrin-G accumulation in distinct spine subdomains, where it differentially regulates NMDA receptor-dependent plasticity. These data implicate subsynaptic nanodomains containing a major psychiatric risk molecule, ankyrin-G, as having location-specific functions, and opens directions for basic and translational investigation of psychiatric risk molecules.
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影响因子：
16.2
作者：
Frost, Nicholas A.;Shroff, Hari;Kong, Huihui;Betzig, Eric;Blanpied, Thomas A.
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影响因子：
3.7
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通讯作者：
Craddock, Nick
影响因子：
5.3
作者：
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通讯作者：
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