A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins.
A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to alpha- and beta-neurexins.
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发表时间：
2005
期刊：
影响因子：
16.2
通讯作者：
A. Boucard;Alexander A. Chubykin;D. Comoletti;P. Taylor;T. Südhof
中科院分区：
文献类型：
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作者：
A. Boucard;Alexander A. Chubykin;D. Comoletti;P. Taylor;T. Südhof
先前的研究表明，突触后神经素与突触前β -神经素形成跨突触复合物，但不与突触前α -神经素形成。出乎意料的是，我们现在发现神经素也结合α -神经素，并且神经素1结合α -和β -神经素受到神经素1（在剪接位点B）和神经素（在剪接位点4）的选择性剪接的调节。在神经素1中，剪接位点B是决定α -神经素结合的主开关，但β -神经素的结合在很大程度上不受影响，而神经素的选择性剪接则调节神经素的结合。此外，具有不同神经素结合特性的神经素1剪接变体对突触发生的调节存在差异：仅结合β -神经素的神经素1能有效刺激突触形成，而同时结合α -和β -神经素的神经素1能更有效地促进突触扩张。这些发现表明，与α -和β -神经素结合的神经素介导跨突触细胞粘附，但对突触形成有不同的影响，表明不同的神经素和神经素亚型的表达指定了跨突触信号编码。
Previous studies suggested that postsynaptic neuroligins form a trans-synaptic complex with presynaptic beta-neurexins, but not with presynaptic alpha-neurexins. Unexpectedly, we now find that neuroligins also bind alpha-neurexins and that alpha- and beta-neurexin binding by neuroligin 1 is regulated by alternative splicing of neuroligin 1 (at splice site B) and of neurexins (at splice site 4). In neuroligin 1, splice site B is a master switch that determines alpha-neurexin binding but leaves beta-neurexin binding largely unaffected, whereas alternative splicing of neurexins modulates neuroligin binding. Moreover, neuroligin 1 splice variants with distinct neurexin binding properties differentially regulate synaptogenesis: neuroligin 1 that binds only beta-neurexins potently stimulates synapse formation, whereas neuroligin 1 that binds to both alpha- and beta-neurexins more effectively promotes synapse expansion. These findings suggest that neuroligin binding to alpha- and beta-neurexins mediates trans-synaptic cell adhesion but has distinct effects on synapse formation, indicating that expression of different neuroligin and neurexin isoforms specifies a trans-synaptic signaling code.