A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin
A slowed classical pathway rather than kiss-and-run mediates endocytosis at synapses lacking synaptojanin and endophilin
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DOI：
10.1016/j.cell.2005.09.026
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发表时间：
2005-11-04
期刊：
影响因子：
64.5
通讯作者：
Schwarz, TL
中科院分区：
文献类型：
--
作者：
Dickman, DK;Horne, JA;Schwarz, TL
内吞作用的“吻和跑”模式在多大程度上有助于突触囊泡再循环仍然存在争议。突触上的吻和跑的唯一遗传证据来自于编码synaptojanin和endophilin的基因突变，这两种蛋白在经典的网格蛋白介导的内吞作用中共同起着揭开囊泡外壳的作用。在这里，我们的特点是内吞作用，持续在果蝇synaptojanin和endophilin无效等位基因。在高频刺激下，这些突变体的突触囊泡池可以可逆地耗尽。从这种消耗中恢复是缓慢的，表明经典内吞作用受损形式的持续存在。稳态胞吐率表明，内吞饱和突变神经肌肉末梢在80囊泡/秒，10%-20%的野生型率。量子大小，FM 1 -43加载，和发动蛋白功能的分析进一步表明，即使在没有synaptojanin或endophilin囊泡进行充分融合和重新形成。因此，没有遗传学证据表明突触囊泡经历亲吻和逃跑。
The extent to which a "kiss-and-run" mode of endocytosis contributes to synaptic-vesicle recycling remains controversial. The only genetic evidence for kiss-and-run at the synapse comes from mutations in the genes encoding synaptojanin and endophilin, proteins that together function to uncoat vesicles in classical clathrin-mediated endocytosis. Here we have characterized the endocytosis that persists in null alleles of Drosophila synaptojanin and endophilin. In response to high-frequency stimulation, the synaptic-vesicle pool can be reversibly depleted in these mutants. Recovery from this depletion is slow and indicates the persistence of an impaired form of classical endocytosis. Steady-state exocytosis rates reveal that endocytosis saturates in mutant neuromuscular terminals at 80 vesicles/s, 10%-20% of the wild-type rate. Analyses of quantal size, FM1-43 loading, and dynamin function further demonstrate that even in the absence of synaptojanin or endophilin vesicles undergo full fusion and re-formation. Therefore, no genetic evidence remains to indicate that synaptic vesicles undergo kiss-and-run.