Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites.
Identification of Proteins Required for Precise Positioning of Apc2 in Dendrites.
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DOI：
10.1534/g3.118.200205
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发表时间：
2018-05-04
期刊：
影响因子：
--
通讯作者：
Rolls MM
中科院分区：
文献类型：
--
作者：
Weiner AT;Seebold DY;Michael NL;Guignet M;Feng C;Follick B;Yusko BA;Wasilko NP;Torres-Gutierrez P;Rolls MM
在果蝇神经元中，树突中一致的负端出极性部分是通过驱动蛋白2介导的在分支点生长微管的转向来维持的。Apc将驱动蛋白马达连接到生长的微管加端，Apc 2将Apc募集到其发挥功能的分支点。由于Apc 2的作用是将其他操纵蛋白集中到分支点，因此我们希望了解Apc 2是如何靶向的。从最初的广泛候选RNAi筛选中，我们发现Miro（线粒体转运蛋白）、Ank 2、Axin、spastin和Rac 1是将Apc 2-GFP定位在树突分支点所必需的。YFP-Ank 2-L 8、Axin-GFP和线粒体也定位于分支点，表明筛选鉴定了相关蛋白。通过进行二次筛选，我们发现线粒体的能量产生是Apc 2-GFP定位的关键，而spastin作用于线粒体的上游。Ank 2似乎独立于其他参与者，除了它的膜伙伴神经胶质细胞（Nrg）。Rac 1可能通过Arp 2/3产生分支肌动蛋白来帮助招募Apc 2-GFP。Axin可以在多种wnt信号通路中发挥作用，其中之一包括异源三聚体G蛋白和Frizzleds。Gαs、Gαo、Fz和Fz 2的敲除减少了Apc 2和Axin对分支点的靶向。总的来说，我们的数据表明，线粒体能量的产生，Nrg/Ank 2，由Arp 2/3和Fz/G蛋白/Axin产生的分支肌动蛋白功能作为四个模块，控制微管调节Apc 2的本地化到其在树突分支点的作用位点。
In Drosophila neurons, uniform minus-end-out polarity in dendrites is maintained in part by kinesin-2-mediated steering of growing microtubules at branch points. Apc links the kinesin motor to growing microtubule plus ends and Apc2 recruits Apc to branch points where it functions. Because Apc2 acts to concentrate other steering proteins to branch points, we wished to understand how Apc2 is targeted. From an initial broad candidate RNAi screen, we found Miro (a mitochondrial transport protein), Ank2, Axin, spastin and Rac1 were required to position Apc2-GFP at dendrite branch points. YFP-Ank2-L8, Axin-GFP and mitochondria also localized to branch points suggesting the screen identified relevant proteins. By performing secondary screens, we found that energy production by mitochondria was key for Apc2-GFP positioning and spastin acted upstream of mitochondria. Ank2 seems to act independently from other players, except its membrane partner, Neuroglian (Nrg). Rac1 likely acts through Arp2/3 to generate branched actin to help recruit Apc2-GFP. Axin can function in a variety of wnt signaling pathways, one of which includes heterotrimeric G proteins and Frizzleds. Knockdown of Gαs, Gαo, Fz and Fz2, reduced targeting of Apc2 and Axin to branch points. Overall our data suggest that mitochondrial energy production, Nrg/Ank2, branched actin generated by Arp2/3 and Fz/G proteins/Axin function as four modules that control localization of the microtubule regulator Apc2 to its site of action in dendrite branch points.
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影响因子：
4.5
作者：
Jegla T;Nguyen MM;Feng C;Goetschius DJ;Luna E;van Rossum DB;Kamel B;Pisupati A;Milner ES;Rolls MM
通讯作者：
Rolls MM
影响因子：
3
作者：
Baas PW;Lin S
通讯作者：
Lin S
影响因子：
14.9
作者：
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通讯作者：
the FlyBase Consortium
影响因子：
9.2
作者：
Cliffe, A;Hamada, F;Bienz, M
通讯作者：
Bienz, M
影响因子：
7.2
作者：
Cadigan, Ken M.;Peifer, Mark
通讯作者：
Peifer, Mark