Anterograde Transport of Rab4-Associated Vesicles Regulates Synapse Organization in Drosophila.
Anterograde Transport of Rab4-Associated Vesicles Regulates Synapse Organization in Drosophila.
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DOI：
10.1016/j.celrep.2017.02.034
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发表时间：
2017-03-07
期刊：
影响因子：
8.8
通讯作者：
Ray K
中科院分区：
文献类型：
--
作者：
Dey S;Banker G;Ray K
突触的局部内体回收对于维持神经传递至关重要。 Rab4GTPase 是在分选内涵体时发现的，被认为可以平衡突触前区室中内吞、再循环和降解途径之间的囊泡流动。在这里，我们报告 Rab4 相关囊泡在果蝇轴突中双向移动，但具有顺行偏向，导致它们在幼虫腹侧神经节的突触区域适度富集。大鼠胚胎成纤维细胞中的 FRB-FKBP 缀合测定结果以及果蝇中的遗传分析表明，与 Kinesin-2 的关联（由 Kinesin-2α/KIF3A/KLP64D 亚基的尾部结构域介导）可将 Rab4 相关囊泡移向突触。 Rab4 顺行交通的减少导致腹侧神经节中突触承载区域的体积扩大，并增加果蝇幼虫的运动性。这些结果表明，Rab4 依赖性囊泡向突触的运输在维持该神经元网络中的突触平衡方面发挥着至关重要的作用。戴伊等人。研究表明，在果蝇幼虫中，与驱动蛋白 2α 尾部的结合将 Rab4 相关囊泡推向突触。 Rab4 运输减少会扩大腹侧神经节的突触承载区域并增强幼虫的运动性。因此，Kinesin-2 介导的 Rab4 运输似乎可以调节神经元网络中的突触稳态。内体运输和神经元运输的物流。新生的 Rab4 囊泡是分选中间内体的一部分，显示与驱动蛋白-2α (KIF3A/KLP64D) 尾部结合。 Rab4 相关囊泡主要由果蝇轴突中的异源三聚体驱动蛋白-2 转运。建议将这些囊泡的一部分与驱动蛋白 3 家族马达 Khc-73 结合，以促进它们的突触前传递。这种运输在抑制突触组装、维持果蝇幼虫大脑的稳态方面发挥着至关重要的作用。
Local endosomal recycling at synapses is essential to maintain neurotransmission. Rab4GTPase, found on sorting endosomes, is proposed to balance the flow of vesicles between endocytic, recycling and degradative pathways in the presynaptic compartment. Here, we report that Rab4-associated vesicles move bidirectionally in Drosophila axons but with an anterograde bias, resulting in their moderate enrichment at the synaptic region of the larval ventral ganglion. Results from FRB-FKBP conjugation assays in rat embryonic fibroblasts together with genetic analyses in Drosophila indicate that an association with Kinesin-2 (mediated by the tail domain of Kinesin-2α/KIF3A/KLP64D subunit) moves Rab4-associated vesicles towards the synapse. Reduction in the anterograde traffic of Rab4 causes an expansion of the volume of the synapse-bearing region in the ventral ganglion and increases the motility of Drosophila larvae. These results suggest that Rab4-dependent vesicular traffic towards the synapse plays a vital role in maintaining synaptic balance in this neuronal network. Dey et.al. show that in Drosophila larvae, binding to the Kinesin-2α tail propels Rab4-associated vesicles towards the synapse. Reduced Rab4 transport expands the synapse-bearing region of the ventral ganglion and enhances larval motility. Hence, Kinesin-2 mediated Rab4 trafficking appears to regulate synapse homeostasis in a neuronal network. The logistics of endosomal transport and trafficking in neurons. The nascent Rab4 vesicles, a part of the sorting intermediate endosomes, are shown to bind to Kinesin-2α (KIF3A/KLP64D) tail. Rab4-associated vesicles are transported predominantly by heterotrimeric Kinesin-2 in Drosophila axons. Association of a fraction of these vesicles with a Kinesin-3 family motor, Khc-73, is suggested to facilitate their pre-synaptic delivery. This transport is indicated to play a crucial role in suppressing the synapse assembly, maintaining homeostasis in the Drosophila larval brain.