The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis
The CHD Protein, Kismet, is Important for the Recycling of Synaptic Vesicles during Endocytosis
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DOI：
10.1038/s41598-019-55900-6
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发表时间：
2019-12-18
影响因子：
4.6
通讯作者：
Liebl, Faith L. W.
中科院分区：
文献类型：
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作者：
Latcheva, Nina K.;Delaney, Taylor L.;Liebl, Faith L. W.
染色体结构域DNA结合蛋白家族的染色质重塑蛋白质CHD 7和CHD 8介导早期神经发育事件，包括神经迁移和分化。因此，任何一种蛋白质的突变都可能导致神经发育障碍。然而，染色质重塑蛋白如何影响成熟突触的活性相对未被探索。成熟神经元的一个关键特征是调节良好的内吞作用，这对于突触功能回收膜和突触蛋白使得能够持续释放突触囊泡是至关重要的。在这里，我们表明，Kismet，果蝇同系物的CHD 7和CHD 8，调节内吞作用。Kismet积极影响转录水平和绑定到dap 160和endophilin B转录起始位点和启动子在整个神经系统中，并影响突触定位的发动蛋白/Shibire。此外，kismet突变体表现出减少VGLUT，突触囊泡标记，在刺激，但不是静息突触和突触Rab 11水平降低。通过抑制组蛋白脱乙酰基转移酶（HDAC）的功能，在kismet突变突触中恢复内吞作用。这些数据表明，HDAC活性可能会反对Kismet促进突触囊泡内吞作用。更深入地了解CHD蛋白如何调节成熟神经元的功能将有助于更好地了解神经发育障碍。
Chromatin remodeling proteins of the chromodomain DNA-binding protein family, CHD7 and CHD8, mediate early neurodevelopmental events including neural migration and differentiation. As such, mutations in either protein can lead to neurodevelopmental disorders. How chromatin remodeling proteins influence the activity of mature synapses, however, is relatively unexplored. A critical feature of mature neurons is well-regulated endocytosis, which is vital for synaptic function to recycle membrane and synaptic proteins enabling the continued release of synaptic vesicles. Here we show that Kismet, the Drosophila homolog of CHD7 and CHD8, regulates endocytosis. Kismet positively influenced transcript levels and bound to dap160 and endophilin B transcription start sites and promoters in whole nervous systems and influenced the synaptic localization of Dynamin/Shibire. In addition, kismet mutants exhibit reduced VGLUT, a synaptic vesicle marker, at stimulated but not resting synapses and reduced levels of synaptic Rab11. Endocytosis is restored at kismet mutant synapses by pharmacologically inhibiting the function of histone deacetyltransferases (HDACs). These data suggest that HDAC activity may oppose Kismet to promote synaptic vesicle endocytosis. A deeper understanding of how CHD proteins regulate the function of mature neurons will help better understand neurodevelopmental disorders.