Marie Bruno, Sweeney Sean T, Poskanzer Kira E, Roos Jack, Kelly Regis B, Davis Graeme W
Department of Biochemistry and Biophysics, 1550 4th Street, GDBS Fourth Floor North, University of California, San Francisco, 94143, USA.
Neuron. 2004 Jul 22;43(2):207-19. doi: 10.1016/j.neuron.2004.07.001.
Dap160/Intersectin is a multidomain adaptor protein that colocalizes with endocytic machinery in the periactive zone at the Drosophila NMJ. We have generated severe loss-of-function mutations that eliminate Dap160 protein from the NMJ. dap160 mutant synapses have decreased levels of essential endocytic proteins, including dynamin, endophilin, synaptojanin, and AP180, while other markers of the active zone and periactive zone are generally unaltered. Functional analyses demonstrate that dap160 mutant synapses are unable to sustain high-frequency transmitter release, show impaired FM4-64 loading, and show a dramatic increase in presynaptic quantal size consistent with defects in synaptic vesicle recycling. The dap160 mutant synapse is grossly malformed with abundant, highly ramified, small synaptic boutons. We present a model in which Dap160 scaffolds both endocytic machinery and essential synaptic signaling systems to the periactive zone to coordinately control structural and functional synapse development.
Dap160/Intersectin是一种多结构域衔接蛋白，它与果蝇神经肌肉接头（NMJ）活性区周围的内吞机制共定位。我们已经产生了严重的功能丧失突变，这些突变从NMJ中消除了Dap160蛋白。dap160突变体突触中包括发动蛋白、内吞蛋白、突触素和AP180在内的必需内吞蛋白水平降低，而活性区和活性区周围的其他标记物通常未改变。功能分析表明，dap160突变体突触无法维持高频递质释放，显示FM4-64加载受损，并显示突触前量子大小显著增加，这与突触小泡循环缺陷一致。dap160突变体突触严重畸形，有大量高度分支的小突触小体。我们提出了一个模型，其中Dap160将内吞机制和必需的突触信号系统搭建到活性区周围，以协调控制突触的结构和功能发育。
