Varoqueaux Frédérique, Jamain Stéphane, Brose Nils
Max-Planck-Institute for Experimental Medicine, Department of Molecular Neurobiology, Göttingen, Germany.
Eur J Cell Biol. 2004 Sep;83(9):449-56. doi: 10.1078/0171-9335-00410.
Neuroligins are cell adhesion proteins that are thought to instruct the formation and alignment of synaptic specializations. The three known rodent neuroligin isoforms share homologous extracellular acetylcholinesterase-like domains that bridge the synaptic cleft and bind beta-neurexins. All neuroligins have identical intracellular C-terminal motifs that bind to PDZ domains of various target proteins. Neuroligin 1 is specifically localized to glutamatergic postsynaptic specializations. We show here that neuroligin 2 is exclusively localized to inhibitory synapses in rat brain and dissociated neurons. In immature neurons, neuroligin 2 is found at synapses and also at GABAA receptor aggregates that are not facing presynaptic termini, indicating that postsynaptic mechanisms lead to synaptic recruitment of neuroligin 2. Our findings identify neuroligin 2 as a new cell adhesion protein specific for inhibitory synapses and open new avenues for identifiying the constituents of this unique type of postsynaptic specialization.
神经连接蛋白是细胞粘附蛋白，被认为在指导突触特化的形成和排列中发挥作用。已知的三种啮齿动物神经连接蛋白亚型具有同源的细胞外乙酰胆碱酯酶样结构域，该结构域跨越突触间隙并与β-神经突触素结合。所有神经连接蛋白都具有相同的细胞内C末端基序，可与各种靶蛋白的PDZ结构域结合。神经连接蛋白1特异性定位于谷氨酸能突触后特化部位。我们在此表明，神经连接蛋白2仅定位于大鼠脑和离体神经元的抑制性突触。在未成熟神经元中，神经连接蛋白2存在于突触以及不面对突触前末端的GABAA受体聚集体中，这表明突触后机制导致神经连接蛋白2的突触募集。我们的研究结果确定神经连接蛋白2是一种新的特异性针对抑制性突触的细胞粘附蛋白，并为鉴定这种独特类型突触后特化的组成成分开辟了新途径。
