Department of Biology, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Cell Biol. 2011 Apr 4;193(1):201-17. doi: 10.1083/jcb.201009052.
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.
针对生长信号的突触结构重塑导致许多系统中的神经元功能发生持久改变。突触生长因子受体在通过内吞途径运输时改变其信号特性，但控制内吞隔室之间货物运输的机制仍不清楚。Nwk（神经破坏）是一种突触前 F-BAR/SH3 蛋白，它在黑腹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（SNX16）的物理相互作用发挥作用。SNX16 通过激活骨形态发生蛋白受体促进突触生长信号，神经元的实时成像显示 SNX16 阳性早期内体与含有 Nwk 的再循环内体之间发生短暂相互作用。我们确定了一种替代的信号终止途径，在没有 Snx16 的情况下，该途径受内体分选复合物必需的运输（ESCRT）介导的受体内化到内体腔中的控制。我们的结果定义了一种由 SNX16、NWK 和 ESCRT 复合物介导的突触前运输途径，该途径在内体隔室之间的界面处起作用，以控制突触生长信号。
