Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Cell Rep. 2012 Jul 26;2(1):101-10. doi: 10.1016/j.celrep.2012.06.009. Epub 2012 Jul 20.
Polymorphic adhesion molecules neurexin and neuroligin (NL) mediate asymmetric trans-synaptic adhesion, which is crucial for synapse development and function. It is not known whether or how individual synapse function is controlled by the interactions between variants and isoforms of these molecules with differing ectodomain regions. At a physiological concentration of Ca(2+), the ectodomain complex of neurexin-1 β isoform (Nrx1β) and NL1 spontaneously assembled into crystals of a lateral sheet-like superstructure topologically compatible with transcellular adhesion. Correlative light-electron microscopy confirmed extracellular sheet formation at the junctions between Nrx1β- and NL1-expressing non-neuronal cells, mimicking the close, parallel synaptic membrane apposition. The same NL1-expressing cells, however, did not form this higher-order architecture with cells expressing the much longer neurexin-1 α isoform, suggesting a functional discrimination mechanism between synaptic contacts made by different isoforms of neurexin variants.
多态性黏附分子神经连接蛋白和神经黏附素（NL）介导不对称的突触间黏附，这对突触的发育和功能至关重要。目前尚不清楚个体突触功能是否以及如何受到这些分子的变体和异构体与不同胞外区之间相互作用的控制。在生理浓度的 Ca（2+）下，神经连接蛋白-1β 异构体（Nrx1β）和 NL1 的胞外域复合物自发组装成具有细胞间黏附拓扑兼容性的横向片状超结构晶体。相关的光电子显微镜证实，在表达 Nrx1β 和 NL1 的非神经元细胞之间的连接处形成了细胞外片状结构，模拟了紧密平行的突触膜对位。然而，具有相同 NL1 表达的细胞不会与表达更长的神经连接蛋白-1α异构体的细胞形成这种更高阶的结构，这表明不同神经连接蛋白变体的不同异构体形成的突触接触存在功能区分机制。
