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内吞作用突变体中突触发育和活性区间距的改变。

Altered synaptic development and active zone spacing in endocytosis mutants.

作者信息

Dickman Dion K, Lu Zhiyuan, Meinertzhagen Ian A, Schwarz Thomas L

机构信息

Division of Neuroscience, Children's Hospital, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Curr Biol. 2006 Mar 21;16(6):591-8. doi: 10.1016/j.cub.2006.02.058.

Abstract

Many types of synapses have highly characteristic shapes and tightly regulated distributions of active zones, parameters that are important to the function of neuronal circuits. The development of terminal arborizations must therefore include mechanisms to regulate the spacing of terminals, the frequency of branching, and the distribution and density of release sites. At present, however, the mechanisms that control these features remain obscure. Here, we report the development of supernumerary or "satellite" boutons in a variety of endocytic mutants at the Drosophila neuromuscular junction. Mutants in endophilin, synaptojanin, dynamin, AP180, and synaptotagmin all show increases in supernumerary bouton structures. These satellite boutons contain releasable vesicles and normal complements of synaptic proteins that are correctly localized within terminals. Interestingly, however, synaptojanin terminals have more active zones per unit of surface area and more dense bodies (T-bars) within these active zones, which may in part compensate for reduced transmission per active zone. The altered structural development of the synapse is selectively encountered in endocytosis mutants and is not observed when synaptic transmission is reduced by mutations in glutamate receptors or when synaptic transmission is blocked by tetanus toxin. We propose that endocytosis plays a critical role in sculpting the structure of synapses, perhaps through the endocytosis of unknown regulatory signals that organize morphogenesis at synaptic terminals.

摘要

许多类型的突触具有高度特征性的形状以及活性区分布受到严格调控,这些参数对于神经回路的功能至关重要。因此,终末分支的发育必须包含调控终末间距、分支频率以及释放位点分布和密度的机制。然而目前,控制这些特征的机制仍不清楚。在此,我们报道了在果蝇神经肌肉接头处的多种内吞突变体中出现了多余的或“卫星”型突触小体。内吞蛋白、突触素、发动蛋白、AP180和突触结合蛋白的突变体均显示出多余突触小体结构增加。这些卫星型突触小体含有可释放的囊泡以及正确定位于终末内的正常突触蛋白成分。然而,有趣的是,突触素终末每单位表面积具有更多的活性区,并且在这些活性区内有更密集的小体(T形杆),这可能部分补偿了每个活性区传递的减少。突触结构的改变发育在胞吞作用突变体中选择性出现,而当谷氨酸受体突变导致突触传递减少或破伤风毒素阻断突触传递时则未观察到。我们提出,内吞作用在塑造突触结构中起关键作用,可能是通过内吞未知的调控信号来组织突触终末的形态发生。

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