Institute for Neuro- and Sensory Physiology, Heinrich-Heine-University Düsseldorf, Germany.
Neurosci Lett. 2011 Sep 1;501(3):167-72. doi: 10.1016/j.neulet.2011.07.009. Epub 2011 Jul 18.
Classical cadherins are cell adhesion molecules that are thought to contribute to the control of synapse formation, synaptic transmission, and synaptic plasticity. This is largely based on studies investigating the functions of N-cadherin at glutamatergic synapses, whereas other classical cadherins have hardly been examined at central synapses. We have now used a conditional knockout approach in cultured cortical neurons to address the role of E-cadherin mainly at inhibitory, GABAergic synapses. Cortical neurons were cultured from mouse fetuses carrying floxed E-cadherin alleles in homozygous configuration. E-cadherin knockout was induced in individual neurons by expression of an EGFP-Cre fusion protein. Immunocytochemical stainings for the vesicular GABA (VGAT) and glutamate (VGLUT1) transporters revealed a reduced density of dendritic GABAergic synapses in E-cadherin knockout neurons, whereas glutamatergic synapses were unaffected. Electrophysiological recordings of miniature and action potential-evoked, GABA(A) receptor-mediated postsynaptic currents confirmed an impairment of GABAergic synapses at the functional level. In summary, our immunocytochemical and electrophysiological analysis of E-cadherin knockout neurons suggested that E-cadherin signaling importantly contributes to the regulation of GABAergic synapses in cortical neurons.
经典钙黏蛋白是细胞黏附分子，被认为有助于控制突触形成、突触传递和突触可塑性。这主要基于研究 N-钙黏蛋白在谷氨酸能突触中的功能，而其他经典钙黏蛋白在中枢突触中几乎没有被研究过。我们现在使用条件性基因敲除方法在培养的皮质神经元中研究 E-钙黏蛋白在抑制性 GABA 能突触中的主要作用。从携带纯合 floxed E-钙黏蛋白等位基因的小鼠胚胎中培养皮质神经元。通过表达 EGFP-Cre 融合蛋白，在单个神经元中诱导 E-钙黏蛋白敲除。囊泡 GABA（VGAT）和谷氨酸（VGLUT1）转运体的免疫细胞化学染色显示 E-钙黏蛋白敲除神经元中树突 GABA 能突触的密度降低，而谷氨酸能突触不受影响。对微小和动作电位诱发的 GABA(A)受体介导的突触后电流的电生理记录证实了 GABA 能突触在功能水平上的损伤。总之，我们对 E-钙黏蛋白敲除神经元的免疫细胞化学和电生理分析表明，E-钙黏蛋白信号对皮质神经元中 GABA 能突触的调节有重要贡献。
