Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment.
Bilaterian Giant Ankyrins Have a Common Evolutionary Origin and Play a Conserved Role in Patterning the Axon Initial Segment.
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DOI：
10.1371/journal.pgen.1006457
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发表时间：
2016-12
期刊：
影响因子：
4.5
通讯作者：
Rolls MM
中科院分区：
文献类型：
--
作者：
Jegla T;Nguyen MM;Feng C;Goetschius DJ;Luna E;van Rossum DB;Kamel B;Pisupati A;Milner ES;Rolls MM
在脊椎动物神经元中，轴突起始段（AIS）专门用于动作电位起始。它由锚蛋白G（AnkG）的一个巨大的480 Kd变体组成，该变体充当离子通道的锚，并且是质膜扩散屏障所必需的，该屏障将体树突蛋白从轴突中排除。编码这种480 Kd变体所需的异常长的外显子被认为是最近在脊椎动物进化过程中才插入的，因此基于巨大锚定的AIS支架被视为脊椎动物对快速，精确信号的适应。我们重新研究AIS的进化，通过锚蛋白的基因组分析，并通过测试锚蛋白在模型多极果蝇神经元（ddaE）的近端轴突组织的作用。我们在所有主要的双侧门中发现了巨大的锚蛋白亚型，并提出了支持巨型锚蛋白和相应的长外显子在双侧祖先中的单一共同起源的证据。这一发现提出了一个问题，是否巨大的锚蛋白异构体在AIS组织中发挥保守的作用，整个Bilateria。我们研究了这种可能性，通过寻找保守的锚定依赖AIS功能在果蝇ddaE神经元通过现场成像。我们发现，ddaE神经元有一个轴突扩散屏障近端的细胞体，需要一个巨大的亚型的神经元锚蛋白Ank2。此外，钾离子通道shal集中在近端轴突在Ank2依赖的方式。我们的研究结果表明，巨大的锚为基础的细胞骨架的AIS可能已经进化之前的辐射现存的两侧谱系，比以前认为的要早得多。轴突起始段（AIS）目前被认为是脊椎动物神经元的一个显著特征，使其适应快速，精确的信号传导。它作为神经元兴奋性调节的枢纽，作为动作电位起始的位点，也作为高度特化的轴突和细胞其余部分之间的边界。在这里，我们表明，巨大的锚蛋白，结构组织AIS，并被认为是脊椎动物特有的，而不是有一个古老的起源在一个双侧祖先。我们进一步表明，在果蝇感觉神经元的轴突和索马之间存在一个巨大的依赖于锚定的AIS样质膜边界。这些结果表明，AIS的细胞骨架骨架骨架不是脊椎动物所独有的，而是双侧神经元的进化保守特征。
In vertebrate neurons, the axon initial segment (AIS) is specialized for action potential initiation. It is organized by a giant 480 Kd variant of ankyrin G (AnkG) that serves as an anchor for ion channels and is required for a plasma membrane diffusion barrier that excludes somatodendritic proteins from the axon. An unusually long exon required to encode this 480Kd variant is thought to have been inserted only recently during vertebrate evolution, so the giant ankyrin-based AIS scaffold has been viewed as a vertebrate adaptation for fast, precise signaling. We re-examined AIS evolution through phylogenomic analysis of ankyrins and by testing the role of ankyrins in proximal axon organization in a model multipolar Drosophila neuron (ddaE). We find giant isoforms of ankyrin in all major bilaterian phyla, and present evidence in favor of a single common origin for giant ankyrins and the corresponding long exon in a bilaterian ancestor. This finding raises the question of whether giant ankyrin isoforms play a conserved role in AIS organization throughout the Bilateria. We examined this possibility by looking for conserved ankyrin-dependent AIS features in Drosophila ddaE neurons via live imaging. We found that ddaE neurons have an axonal diffusion barrier proximal to the cell body that requires a giant isoform of the neuronal ankyrin Ank2. Furthermore, the potassium channel shal concentrates in the proximal axon in an Ank2-dependent manner. Our results indicate that the giant ankyrin-based cytoskeleton of the AIS may have evolved prior to the radiation of extant bilaterian lineages, much earlier than previously thought. The axon initial segment (AIS) is currently thought to be a distinguishing feature of vertebrate neurons that adapts them for rapid, precise signaling. It serves as a hub for the regulation of neuronal excitability as the site of action potential initiation and also acts as the boundary between the highly-specialized axon and the rest of the cell. Here we show that the giant ankyrins that structurally organize the AIS, and were thought to be vertebrate-specific, instead have an ancient origin in a bilaterian ancestor. We further show the presence of a giant ankyrin-dependent AIS-like plasma membrane boundary between the axon and soma in a Drosophila sensory neuron. These results suggest that the cytoskeletal backbone for the AIS is not unique to vertebrates, but instead may be an evolutionarily conserved feature of bilaterian neurons.
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影响因子：
12.3
作者：
Fairclough SR;Chen Z;Kramer E;Zeng Q;Young S;Robertson HM;Begovic E;Richter DJ;Russ C;Westbrook MJ;Manning G;Lang BF;Haas B;Nusbaum C;King N
通讯作者：
King N
DOI：
10.1073/pnas.1416544112
发表时间：
2015-01-27
影响因子：
11.1
作者：
Jenkins, Paul M.;Kim, Namsoo;Bennett, Vann
通讯作者：
Bennett, Vann
影响因子：
3.7
作者：
Baker EC;Layden MJ;van Rossum DB;Kamel B;Medina M;Simpson E;Jegla T
通讯作者：
Jegla T
影响因子：
3.5
作者：
Hortsch, M;Paisley, KL;Chandler, R
通讯作者：
Chandler, R
DOI：
10.1083/jcb.109.6.3085
发表时间：
1989-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baas PW;Black MM;Banker GA
通讯作者：
Banker GA