The Making of Neurexins
The Making of Neurexins
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DOI：
10.1046/j.1471-4159.1998.71041339.x
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发表时间：
1998-10
影响因子：
4.7
通讯作者：
M. Missler;R. Fernández-Chacón;T. Südhof
中科院分区：
文献类型：
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作者：
M. Missler;R. Fernández-Chacón;T. Südhof
翻译后摘要：Neurexins是神经元细胞表面蛋白与多达数千种亚型。这些异构体是由三个基因中的六个启动子的转录物的选择性剪接产生的。neurexins的结构类似于细胞表面受体，具有模块化结构，表明进化过程中的顺序组装。神经毒素可能在大脑中执行多种功能。它们参与细胞间连接，其中β-neurexins与第二类神经元细胞表面受体（称为神经配素）紧密结合。在细胞内，neurexin/神经连接蛋白连接在neurexin侧被CASK结合，在神经连接蛋白侧被PSD 95结合。CASK和PSD 95是同源膜相关鸟苷酸激酶，通过PDZ结构域与neurexin/neuroligin连接结合，产生具有相似细胞内结合配偶体的不对称连接（neurexin/neuroligin）。除了作为细胞粘附分子的功能外，neurexins还可以作为信号受体，因为α-neurexins的一类配体称为neurexophilins，类似于肽激素。最后，至少一种neurexin亚型neurexin Iα代表α-latrotoxin的高亲和力受体，α-latrotoxin是一种强效兴奋性神经毒素。因此，neurexins构成了一个大家族的神经元受体，可能参与神经元之间的多种相互作用功能。
Abstract: Neurexins are neuronal cell‐surface proteins with up to thousands of isoforms. These isoforms are generated by alternative splicing of transcripts from six promoters in three genes. The structure of neurexins resembles cell‐surface receptors with a modular architecture suggestive of a sequential assembly during evolution. Neurexins probably perform multiple functions in the brain. They participate in intercellular junctions in which β‐neurexins tightly bind to a second class of neuronal cell‐surface receptors called neuroligins. Intracellularly, the neurexin/neuroligin junction is bound by CASK on the neurexin side and PSD95 on the neuroligin side. CASK and PSD95 are homologous membrane‐associated guanylate kinases that bind to the neurexin/neuroligin junction via PDZ domains, creating an asymmetric junction (neurexin/neuroligin) with similar intracellular binding partners. In addition to a function as cell‐adhesion molecules, neurexins may also serve as a signalling receptor, because a class of ligands for α‐neurexins called neurexophilins is similar to peptide hormones. Finally, at least one neurexin isoform, neurexin Iα, represents a high‐affinity receptor for α‐latrotoxin, which is a potent excitatory neurotoxin. Thus, neurexins constitute a large family of neuronal receptors that may be involved in multiple interactive functions between neurons.