Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation
Neuroligin-1 performs neurexin-dependent and neurexin-independent functions in synapse validation
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DOI：
10.1038/emboj.2009.249
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发表时间：
2009-10-21
期刊：
影响因子：
11.4
通讯作者：
Suedhof, Thomas C.
中科院分区：
文献类型：
--
作者：
Ko, Jaewon;Zhang, Chen;Suedhof, Thomas C.
突触后神经配蛋白被认为通过结合突触前α-和β-神经毒素并使其二聚化而在突触确认和突触传递中发挥重要功能。为了验证这一假设，我们研究了神经连接素-1突变的功能影响，这些突变仅损害α-neurexin结合，阻断α-和β-neurexin结合，或消除神经连接素-1二聚化。在所谓的人工突触形成试验中，废除α-neurexin结合废除了在转染的非神经元细胞上神经元突触的神经木质素诱导的产生，即使保留了β-neurexin结合。因此，在该测定中，神经连接素-1通过结合突触前α-神经毒素诱导明显的突触形成。然而，在转染的神经元中，无论是α-还是β-neurexin结合对于突触后神经连接素-1显着增加突触密度的能力都是必不可少的，这表明突触形成的neurexin独立机制。此外，neuroligin-1的二聚化是不需要的非神经元或神经元突触形成测定。然而，α-neurexin结合和neuroligin-1二聚化对于在转染的神经元中由neuroligin-1诱导的表观突触大小的增加是必不可少的。因此，神经连接蛋白-1通过包括作为α-神经连接蛋白结合和神经连接蛋白二聚化的必要组分的机制执行不同的突触功能，但延伸超出这些活动。The EMBO Journal（2009）28，3244-3255. doi：10.1038/doj.2009.249; 2009年9月3日在线发布
Postsynaptic neuroligins are thought to perform essential functions in synapse validation and synaptic transmission by binding to, and dimerizing, presynaptic alpha- and beta-neurexins. To test this hypothesis, we examined the functional effects of neuroligin-1 mutations that impair only alpha-neurexin binding, block both alpha- and beta-neurexin binding, or abolish neuroligin-1 dimerization. Abolishing alpha-neurexin binding abrogated neuroligin-induced generation of neuronal synapses onto transfected non-neuronal cells in the so-called artificial synapse-formation assay, even though beta-neurexin binding was retained. Thus, in this assay, neuroligin-1 induces apparent synapse formation by binding to presynaptic alpha-neurexins. In transfected neurons, however, neither alpha- nor beta-neurexin binding was essential for the ability of postsynaptic neuroligin-1 to dramatically increase synapse density, suggesting a neurexin-independent mechanism of synapse formation. Moreover, neuroligin-1 dimerization was not required for either the non-neuronal or the neuronal synapse-formation assay. Nevertheless, both alpha-neurexin binding and neuroligin-1 dimerization were essential for the increase in apparent synapse size that is induced by neuroligin-1 in transfected neurons. Thus, neuroligin-1 performs diverse synaptic functions by mechanisms that include as essential components of alpha-neurexin binding and neuroligin dimerization, but extend beyond these activities. The EMBO Journal (2009) 28, 3244-3255. doi:10.1038/emboj.2009.249; Published online 3 September 2009