Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, Germany.
Sci Rep. 2017 Jan 20;7:40865. doi: 10.1038/srep40865.
At synapses in the mammalian brain, continuous information transfer requires the long-term maintenance of homeostatic coupling between exo- and endocytosis of synaptic vesicles. Because classical endocytosis is orders of magnitude slower than the millisecond-range exocytosis of vesicles, high frequency vesicle fusion could potentially compromise structural stability of synapses. However, the molecular mechanisms mediating the tight coupling of exo- and endocytosis are largely unknown. Here, we investigated the role of the transsynaptic adhesion molecules N-cadherin and Neuroligin1 in regulating vesicle exo- and endocytosis by using activity-induced FM4-64 staining and by using synaptophysin-pHluorin fluorescence imaging. The synaptic adhesion molecules N-cadherin and Neuroligin1 had distinct impacts on exo- and endocytosis at mature cortical synapses. Expression of Neuroligin1 enhanced vesicle release in a N-cadherin-dependent way. Most intriguingly, expression of N-cadherin enhanced both vesicle exo- and endocytosis. Further detailed analysis of N-cadherin knockout neurons revealed that the boosting of endocytosis by N-cadherin was largely dependent on preceding high levels of vesicle release activity. In summary, regulation of vesicle endocytosis was mediated at the molecular level by N-cadherin in a release activity-dependent manner. Because of its endocytosis enhancing function, N-cadherin might play an important role in the coupling of vesicle exo- and endocytosis.
在哺乳动物大脑的突触中，持续的信息传递需要维持突触小泡胞吐和胞吞之间的内稳态耦联。由于经典的胞吞作用比囊泡的毫秒级胞吐作用慢几个数量级，因此高频囊泡融合可能会破坏突触的结构稳定性。然而，介导胞吐和胞吞紧密耦联的分子机制在很大程度上尚不清楚。在这里，我们通过使用活性诱导的 FM4-64 染色和突触小泡蛋白-pHluorin 荧光成像，研究了跨突触黏附分子 N-钙黏蛋白和神经黏附素 1 在调节囊泡胞吐和胞吞中的作用。突触黏附分子 N-钙黏蛋白和神经黏附素 1 对成熟皮质突触的囊泡胞吐和胞吞有明显不同的影响。神经黏附素 1 的表达以 N-钙黏蛋白依赖的方式增强囊泡释放。最有趣的是，N-钙黏蛋白的表达增强了囊泡的胞吐和胞吞作用。对 N-钙黏蛋白敲除神经元的进一步详细分析表明，N-钙黏蛋白增强胞吞作用在很大程度上依赖于先前高水平的囊泡释放活性。总之，N-钙黏蛋白通过一种依赖释放活性的方式在分子水平上调节囊泡胞吞作用。由于其增强胞吞的功能，N-钙黏蛋白可能在囊泡胞吐和胞吞的耦联中发挥重要作用。
