CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
CtBP1-Mediated Membrane Fission Contributes to Effective Recycling of Synaptic Vesicles
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DOI：
10.1016/j.celrep.2020.01.079
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发表时间：
2020-02-18
期刊：
影响因子：
8.8
通讯作者：
Fejtova, Anna
中科院分区：
文献类型：
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作者：
Ivanova, Daniela;Imig, Cordelia;Fejtova, Anna
释放的突触囊泡（SV）的补偿性内吞依赖于脂质-蛋白质界面处的协调信号传导。在这里，我们解决的C-末端结合蛋白1（CtBP1），在培养的海马神经元的基因表达和膜运输的普遍存在的调节突触功能。在CtBP1的情况下，突触形成密度更大，并显示SV分布和大小的变化。增加的基础神经传递和增强的突触抑制可归因于较高的囊泡释放概率和较小的分数的释放能力SV，分别。专门针对结构的救援实验表明，虽然突触发生和释放概率由核CtBP 1控制，SV的有效回收依赖于其突触表达。突触前CtBP 1促进代偿性内吞的能力取决于其膜分裂活性和脂质代谢酶PLD 1的激活。因此，CtBP1调节SV回收促进一个宽容的脂质环境的补偿性内吞作用。
Compensatory endocytosis of released synaptic vesicles (SVs) relies on coordinated signaling at the lipid-protein interface. Here, we address the synaptic function of C-terminal binding protein 1 (CtBP1), a ubiquitous regulator of gene expression and membrane trafficking in cultured hippocampal neurons. In the absence of CtBP1, synapses form in greater density and show changes in SV distribution and size. The increased basal neurotransmission and enhanced synaptic depression could be attributed to a higher vesicular release probability and a smaller fraction of release-competent SVs, respectively. Rescue experiments with specifically targeted constructs indicate that, while synaptogenesis and release probability are controlled by nuclear CtBP1, the efficient recycling of SVs relies on its synaptic expression. The ability of presynaptic CtBP1 to facilitate compensatory endocytosis depends on its membrane-fission activity and the activation of the lipid-metabolizing enzyme PLD1. Thus, CtBP1 regulates SV recycling by promoting a permissive lipid environment for compensatory endocytosis.