Alternative splicing of neuroligin regulates the rate of presynaptic differentiation.
Alternative splicing of neuroligin regulates the rate of presynaptic differentiation.
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DOI：
10.1523/jneurosci.2946-10.2010
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发表时间：
2010-08-25
期刊：
影响因子：
--
通讯作者：
Isacoff E
中科院分区：
文献类型：
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作者：
Lee H;Dean C;Isacoff E
神经连接素（NLGs）和神经毒素（NRX）是促进突触形成的重要粘附分子。存在NLG和NRX的多种剪接变体，但其具体功能尚不清楚。在这里，我们报告了表达全长NLG的替代突触后细胞触发了接触轴突中缓慢的突触前分化。相比之下，缺乏插入B的NLG-1版本（NLG-1-ΔB）诱导快速的突触前分化，达到在天然神经元突触处观察到的速率。我们表明，这种加速是由于插入B内的N-连接的糖基化位点的去除。NLG-1ΔB也比全长NLG-1更多地增加神经元-神经元突触处的突触密度。其他突触后粘附蛋白，如N-钙粘蛋白、EphB 2和SynCAM-1，单独或与全长NLG-1组合不会触发快速分化，表明快速突触前分化依赖于NLG-1ΔB与轴突蛋白的独特相互作用。事实上，我们发现NLG-1ΔB募集更多的轴突α-NRX。我们的研究结果表明，α-NRX的参与是在轴-树接触的新位点快速诱导突触的关键。
Neuroligins (NLGs) and Neurexins (NRXs) are important adhesion molecules that promote synapse formation. Multiple splice variants of NLG and NRX exist, but their specific functions are unclear. Here we report that a surrogate postsynaptic cell expressing full-length NLG triggers slow presynaptic differentiation in a contacting axon. In contrast, a version of NLG-1, which lacks insert B (NLG-1-ΔB), induces rapid presynaptic differentiation, reaching the rate seen at native neuronal synapses. We show that this acceleration is due to removal of the N-linked glycosylation site within insert B. NLG-1ΔB also increases synaptic density at neuro-neuronal synapses more than does full-length NLG-1. Other postsynaptic adhesion proteins, such as N-cadherin, EphB2 and SynCAM-1, alone or in combination with full-length NLG-1 do not trigger fast differentiation, suggesting that rapid presynaptic differentiation depends on a unique interaction of NLG-1ΔB with axonal proteins. Indeed, we find that NLG-1ΔB recruits more axonal α-NRX. Our results suggest that the engagement of α-NRX is a key to rapid induction of synapses at new sites of axo-dendritic contact.