Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina
Neuroligin-4 is localized to glycinergic postsynapses and regulates inhibition in the retina
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DOI：
10.1073/pnas.1006946108
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发表时间：
2011-02-15
影响因子：
11.1
通讯作者：
Varoqueaux, Frederique
中科院分区：
文献类型：
--
作者：
Hoon, Mrinalini;Soykan, Tolga;Varoqueaux, Frederique
神经连接蛋白(NL1-NL4)是控制中枢神经系统(CNS)突触成熟和功能的突触后黏附蛋白。NL4功能缺失突变与罕见的单基因遗传性自闭症有关，但其定位和功能尚不清楚。以视网膜为模型系统，我们发现NL4优先定位于甘氨酸能后突触，并且NL4的缺失伴随着介导甘氨酸能快速传递的甘氨酸受体数量的减少。因此，NL4缺陷的神经节细胞表现出较慢的甘氨酸能微小突触后电流和其刺激编码效率的细微变化，通过视网膜电波记录评估，NL4缺陷视网膜网络内的抑制发生改变。这些数据表明，NL4通过调节甘氨酸能抑制来影响视网膜的网络活动和信息处理。重要的是，NL4还靶向于中枢其他区域的抑制性突触，如丘脑、丘脑、脑干和脊髓，并在体内与突触后抑制性蛋白Geporrin和ColyBistin形成复合体，表明NL4是甘氨酸能后突触的重要组成部分。
Neuroligins (NL1-NL4) are postsynaptic adhesion proteins that control the maturation and function of synapses in the central nervous system (CNS). Loss-of-function mutations in NL4 are linked to rare forms of monogenic heritable autism, but its localization and function are unknown. Using the retina as a model system, we show that NL4 is preferentially localized to glycinergic postsynapses and that the loss of NL4 is accompanied by a reduced number of glycine receptors mediating fast glycinergic transmission. Accordingly, NL4-deficient ganglion cells exhibit slower glycinergic miniature postsynaptic currents and subtle alterations in their stimuluscoding efficacy, and inhibition within the NL4-deficient retinal network is altered as assessed by electroretinogram recordings. These data indicate that NL4 shapes network activity and information processing in the retina by modulating glycinergic inhibition. Importantly, NL4 is also targeted to inhibitory synapses in other areas of the CNS, such as the thalamus, colliculi, brainstem, and spinal cord, and forms complexes with the inhibitory postsynapse proteins gephyrin and collybistin in vivo, indicating that NL4 is an important component of glycinergic postsynapses.