Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University Medical School, Stanford, CA 94305, USA.
Science. 2019 Feb 22;363(6429). doi: 10.1126/science.aav7969.
Bidirectional signaling by cell adhesion molecules is thought to mediate synapse formation, but the mechanisms involved remain elusive. We found that the adhesion G protein-coupled receptors latrophilin-2 and latrophilin-3 selectively direct formation of perforant-path and Schaffer-collateral synapses, respectively, to hippocampal CA1-region neurons. Latrophilin-3 binds to two transcellular ligands: fibronectin leucine-rich repeat transmembrane proteins (FLRTs) and teneurins. In transgenic mice in vivo, both binding activities were required for input-specific synapse formation, which suggests that coincident binding of both ligands is necessary for synapse formation. In cultured neurons in vitro, teneurin or FLRT alone did not induce excitatory synapse formation, whereas together they potently did so. Thus, postsynaptic latrophilins promote excitatory synapse formation by simultaneous binding of two unrelated presynaptic ligands, which is required for formation of synaptic inputs at specific dendritic localizations.
细胞黏附分子的双向信号传递被认为介导了突触的形成，但相关机制仍难以捉摸。我们发现黏附 G 蛋白偶联受体 latrophilin-2 和 latrophilin-3 分别选择性地指导穿通通路和 Schaffer 侧枝突触形成到海马 CA1 区神经元。Latrophilin-3 与两种细胞间配体结合：纤维连接蛋白富含亮氨酸重复跨膜蛋白 (FLRTs) 和 tenurins。在体内转基因小鼠中，两种结合活性对于输入特异性突触形成都是必需的，这表明两种配体的同时结合对于突触形成是必要的。在体外培养的神经元中，teneurin 或 FLRT 单独不能诱导兴奋性突触形成，而两者共同作用则能强烈诱导。因此，突触后 latrophilin 通过同时结合两个不相关的突触前配体促进兴奋性突触形成，这对于在特定树突位置形成突触输入是必需的。
