据悉，突触由跨突触粘附分子组织，这些分子协调前后突触特殊结构的组装，后者又由形成液-液相分离凝聚物的支架蛋白组成。前突触teneurin通过与后突触latrophilin结合介导兴奋性突触的组织。然而，teneurin的作用机制，由从细菌毒素演化而来的细胞外结构域驱动，仍不清楚。
研究人员展示了，只有细胞内序列、二聚化序列和源自细菌毒素的外部latrophilin结合域，对于突触组织是必需的，表明teneurin诱导的latrophilin聚集介导了突触发生。细胞内Teneurin-3序列捕捉液-液相分离的前突触活跃区支架，使研究人员能够从纯化蛋白中重建一个完整的突触连接，其中跨突触的teneurin-latrophilin复合物招募了相分离的前后突触特殊结构。
附：英文原文
Title: Reconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes
Author: Xuchen Zhang, Xudong Chen, Daniel Matú, Thomas C. Südhof
Issue&Volume: 2025-01-17
Abstract: Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations, which, in turn, are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, remains unclear. In this work, we show that only the intracellular sequence, a dimerization sequence, and extracellular bacterial toxin–derived latrophilin-binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis. Intracellular Teneurin-3 sequences capture liquid-liquid phase-separated presynaptic active zone scaffolds, enabling us to reconstitute an entire synaptic junction from purified proteins in which trans-synaptic teneurin-latrophilin complexes recruit phase-separated pre- and postsynaptic specializations.
DOI: adq3586
Source: https://www.science.org/doi/10.1126/science.adq3586