Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
Neuron. 2017 Jun 21;94(6):1155-1172.e8. doi: 10.1016/j.neuron.2017.05.022.
The formation of functional synapses requires coordinated assembly of presynaptic transmitter release machinery and postsynaptic trafficking of functional receptors and scaffolds. Here, we demonstrate a critical role of presynaptic cadherin/catenin cell adhesion complexes in stabilizing functional synapses and spines in the developing neocortex. Importantly, presynaptic expression of stabilized β-catenin in either layer (L) 4 excitatory neurons or L2/3 pyramidal neurons significantly upregulated excitatory synaptic transmission and dendritic spine density in L2/3 pyramidal neurons, while its sparse postsynaptic expression in L2/3 neurons had no such effects. In addition, presynaptic β-catenin expression enhanced release probability of glutamatergic synapses. Newly identified β-catenin-interacting protein p140Cap is required in the presynaptic locus for mediating these effects. Together, our results demonstrate that cadherin/catenin complexes stabilize functional synapses and spines through anterograde signaling in the neocortex and provide important molecular evidence for a driving role of presynaptic components in spinogenesis in the neocortex.
功能性突触的形成需要协调的突触前递质释放机制和功能性受体和支架的突触后运输。在这里，我们证明了突触前钙粘蛋白/连环蛋白细胞黏附复合物在稳定发育中的新皮层中的功能性突触和棘突中的关键作用。重要的是，稳定的β-连环蛋白在兴奋性神经元或 L2/3 锥体神经元中的层 (L) 4 中的突触前表达显著地上调了 L2/3 锥体神经元中的兴奋性突触传递和树突棘密度，而其在 L2/3 神经元中的稀疏的突触后表达则没有这种效果。此外，突触前β-连环蛋白表达增强了谷氨酸能突触的释放概率。新鉴定的β-连环蛋白相互作用蛋白 p140Cap 在突触前位置对于介导这些效应是必需的。总之，我们的结果表明，钙粘蛋白/连环蛋白复合物通过新皮层中的顺行信号稳定功能性突触和棘突，并为突触前成分在新皮层中的棘突发生中的驱动作用提供了重要的分子证据。
