Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis
Dap160/intersectin acts as a stabilizing scaffold required for synaptic development and vesicle endocytosis
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DOI：
10.1016/j.neuron.2004.06.029
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发表时间：
2004-07-22
期刊：
影响因子：
16.2
通讯作者：
Bellen, HJ
中科院分区：
文献类型：
--
作者：
Koh, TW;Verstreken, P;Bellen, HJ
我们描述了动力蛋白相关蛋白160 kDa(Dap160)突变的分离，dap160是交叉素的果蝇同源物，推测是参与内吞作用、细胞骨架调节和信号传递的蛋白质的适配器。我们发现，部分功能丧失突变体表现出温度敏感型(Ts)麻痹，而零突变体表现出吞噬功能的ts缺陷。功能丧失突变体在幼虫神经肌肉接头(NMJ)表现出过度生长，但诱发的神经传递是正常的。突变的NMJ在22℃时表现出轻微的内吞缺陷，在34℃时明显增强。在Dap160突变的NMJ中，动力蛋白、突触素和内嗜素的水平严重降低，这表明Dap160起到稳定细胞内大分子复合体的作用。电子显微镜显示突变末端的小泡较少，异常的大小泡，并在活动区和周围活动区聚集了内吞中间体。我们的数据表明，Dap160和Dynamin一样，参与了活动区和周围活动区突触小泡的提取。
We describe the isolation of mutations in dynamin-associated protein 160 kDa (dap160), the Drosophila homolog of intersectin, a putative adaptor for proteins involved in endocytosis, cytoskeletal regulation, and signaling. We show that partial loss-of-function mutants display temperature-sensitive (ts) paralysis, whereas null mutants show ts defects in endocytosis. Loss-of-function mutants exhibit bouton overgrowth at larval neuromuscular junctions (NMJs), but evoked neurotransmission is normal. Mutant NMJs show a mild endocytic defect at 22degreesC, which is strongly enhanced at 34degreesC. The levels of dynamin, synaptojanin and endophilin are severely reduced in dap160 mutant NMJs, suggesting that Dap160 serves to stabilize an endocytic macromolecular complex. Electron microscopy reveals fewer vesicles, aberrant large vesicles, and an accumulation of endocytic intermediates at active and periactive zones in mutant terminals. Our data suggest that Dap160, like dynamin, is involved in synaptic vesicle retrieval at active and periactive zones.