A presynaptic endosomal trafficking pathway controls synaptic growth signaling.

A presynaptic endosomal trafficking pathway controls synaptic growth signaling.
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DOI:
10.1083/jcb.201009052
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发表时间:
2011-04-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Littleton JT
Littleton JT
中科院分区:
其他
文献类型:
--
作者:
Rodal AA;Blunk AD;Akbergenova Y;Jorquera RA;Buhl LK;Littleton JT

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Nwk与SNX 16的结合促进早期和回收内体之间界面处突触生长信号的下调。在许多系统中,响应于生长信号的突触的结构重塑导致神经元功能的长期改变。突触生长因子受体在通过内吞途径转运过程中改变其信号传导特性,但控制内吞区室之间货物运输的机制仍不清楚。Nwk(Nervous Wreck)是一种突触前F-BAR/SH 3蛋白,在果蝇中调节突触生长信号。在本文中,我们表明,Nwk通过与分选连接蛋白16(SNX 16)的物理相互作用起作用。SNX 16通过激活的骨形态发生蛋白受体促进突触生长信号传导,神经元中的活体成像揭示SNX 16阳性早期内体与含有Nwk的再循环内体进行短暂的相互作用。我们确定了一个替代信号终止途径的Snx 16的情况下,控制所需的运输(ESCRT)介导的受体内化到内体腔的内体分选复合物。我们的研究结果定义了一个由SNX 16,NWK和ESCRT复合物介导的突触前运输途径,其功能是控制内体隔室之间界面处的突触生长信号。
Association of Nwk with SNX16 promotes down-regulation of synaptic growth signaling at the interface between early and recycling endosomes. Structural remodeling of synapses in response to growth signals leads to long-lasting alterations in neuronal function in many systems. Synaptic growth factor receptors alter their signaling properties during transit through the endocytic pathway, but the mechanisms controlling cargo traffic between endocytic compartments remain unclear. Nwk (Nervous Wreck) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila melanogaster. In this paper, we show that Nwk acts through a physical interaction with sorting nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated bone morphogenic protein receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwk-containing recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by endosomal sorting complex required for transport (ESCRT)–mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX16, NWK, and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments.
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