Neuroligin 2 Drives Postsynaptic Assembly at Perisomatic Inhibitory Synapses through Gephyrin and Collybistin
Neuroligin 2 Drives Postsynaptic Assembly at Perisomatic Inhibitory Synapses through Gephyrin and Collybistin
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DOI：
10.1016/j.neuron.2009.08.023
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发表时间：
2009-09-10
期刊：
影响因子：
16.2
通讯作者：
Varoqueaux, Frederique
中科院分区：
文献类型：
--
作者：
Poulopoulos, Alexandros;Aramuni, Gayane;Varoqueaux, Frederique
在哺乳动物中枢神经系统中，每个神经元通常从不同类别的神经元接收数千个突触输入。突触传递到突触后神经元依赖于质膜的局部和递质特异性分化，突触后受体、支架和粘附蛋白在突触前递质释放位点精确并置积累。我们确定了突触粘附分子神经连接素2的蛋白质相互作用，其驱动抑制性突触的突触后分化。神经连接素2通过保守的细胞质基序结合支架蛋白桥蛋白，并作为collybistin的特异性激活剂发挥作用，从而引导抑制性突触后支架的膜束缚。复合物的神经配素2，桥蛋白和collybistin是足够的细胞自主集群的抑制性神经递质受体。在小鼠中，神经配素2的缺失扰乱GABA能和甘氨酸能突触传递，并导致突触后特化的丧失，特别是在体周抑制性突触。
In the mammalian CNS, each neuron typically receives thousands of synaptic inputs from diverse classes of neurons. Synaptic transmission to the postsynaptic neuron relies on localized and transmitter-specific differentiation of the plasma membrane with postsynaptic receptor, scaffolding, and adhesion proteins accumulating in precise apposition to presynaptic sites of transmitter release. We identified protein interactions of the synaptic adhesion molecule neuroligin 2 that drive postsynaptic differentiation at inhibitory synapses. Neuroligin 2 binds the scaffolding protein gephyrin through a conserved cytoplasmic motif and functions as a specific activator of collybistin, thus guiding membrane tethering of the inhibitory postsynaptic scaffold. Complexes of neuroligin 2, gephyrin and collybistin are sufficient for cell-autonomous clustering of inhibitory neurotransmitter receptors. Deletion of neuroligin 2 in mice perturbs GABAergic and glycinergic synaptic transmission and leads to a loss of postsynaptic specializations specifically at perisomatic inhibitory synapses.