Eaton Benjamin A, Fetter Richard D, Davis Graeme W
Department of Biochemistry and Biophysics, San Francisco, California 94143, USA.
Neuron. 2002 May 30;34(5):729-41. doi: 10.1016/s0896-6273(02)00721-3.
We present evidence that synapse retraction occurs during normal synaptic growth at the Drosophila neuromuscular junction (NMJ). An RNAi-based screen to identify the molecular mechanisms that regulate synapse retraction identified Arp-1/centractin, a subunit of the dynactin complex. Arp-1 dsRNA enhances synapse retraction, and this effect is phenocopied by a mutation in P150/Glued, also a dynactin component. The Glued protein is enriched within the presynaptic nerve terminal, and presynaptic expression of a dominant-negative Glued transgene enhances retraction. Retraction is associated with a local disruption of the synaptic microtubule cytoskeleton. Electrophysiological, ultrastructural, and immunohistochemical data support a model in which presynaptic retraction precedes disassembly of the postsynaptic apparatus. Our data suggests that dynactin functions locally within the presynaptic arbor to promote synapse stability.
我们提供的证据表明，在果蝇神经肌肉接头（NMJ）正常的突触生长过程中会发生突触回缩。基于RNA干扰的筛选用于鉴定调节突触回缩的分子机制，该筛选确定了动力蛋白激活蛋白复合物的一个亚基Arp-1/中心肌动蛋白。Arp-1双链RNA增强突触回缩，并且P150/Glued（也是动力蛋白激活蛋白复合物的一个组分）的突变模拟了这种效应。Glued蛋白在突触前神经末梢内富集，并且显性负性Glued转基因的突触前表达增强了回缩。回缩与突触微管细胞骨架的局部破坏有关。电生理、超微结构和免疫组化数据支持一种模型，即突触前回缩先于突触后装置的解体。我们的数据表明，动力蛋白激活蛋白在突触前树突内局部发挥作用以促进突触稳定性。
