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首页> 外文期刊>The European Journal of Neuroscience >Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses.
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Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses.

机译：Neuroligin-3是GABA能和谷氨酸能突触的神经元粘附蛋白。

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摘要

Synaptic adhesion molecules are thought to play a critical role in the formation, function and plasticity of neuronal networks. Neuroligins (NL1-4) are a family of presumptive postsynaptic cell adhesion molecules. NL1 and NL2 isoforms are concentrated at glutamatergic and GABAergic synapses, respectively, but the cellular expression and synaptic localization of the endogenous NL3 and NL4 isoforms are unknown. We generated a panel of NL isoform-specific antibodies and examined the expression, developmental regulation and synaptic specificity of NL3. We found that NL3 was enriched in brain, where NL3 protein levels increased during postnatal development, coinciding with the peak of synaptogenesis. Subcellular fractionation revealed a concentration of NL3 in synaptic plasma membranes and postsynaptic densities. In cultured hippocampal neurons, endogenous NL3 was highly expressed and was localized at both glutamatergic and GABAergic synapses. Clustering of NL3 in hippocampal neurons by neurexin-expressing cells resulted in coaggregation of NL3 with glutamatergic and GABAergic scaffolding proteins. Finally, individual synapses contained colocalized NL2 and NL3 proteins, and coimmunoprecipitation studies revealed the presence of NL1-NL3 and NL2-NL3 complexes in brain extracts. These findings suggest that rodent NL3 is a synaptic adhesion molecule that is a shared component of glutamatergic and GABAergic synapses.
机译：突触粘附分子被认为在神经网络的形成，功能和可塑性中起关键作用。 Neuroligins（NL1-4）是一类推测的突触后细胞粘附分子。 NL1和NL2亚型分别集中在谷氨酸能和GABA能突触上，但是内源性NL3和NL4亚型的细胞表达和突触定位尚不清楚。我们产生了一组NL异构体特异性抗体，并检查了NL3的表达，发育调控和突触特异性。我们发现NL3富集于大脑中，在出生后发育过程中NL3蛋白水平升高，与突触形成的高峰相吻合。亚细胞分级显示突触质膜和突触后密度的NL3浓度。在培养的海马神经元中，内源性NL3高度表达，并位于谷氨酸能和GABA能突触中。神经毒素表达细胞使海马神经元中的NL3聚集，导致NL3与谷氨酸能和GABA能支架蛋白共聚集。最后，单个突触包含共定位的NL2和NL3蛋白，并且共免疫沉淀研究表明脑提取物中存在NL1-NL3和NL2-NL3复合物。这些发现表明，啮齿动物NL3是一种突触粘附分子，是谷氨酸能和GABA能突触的共同成分。

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