A model for generating differences in microtubules between axonal branches depending on the distance from terminals.
A model for generating differences in microtubules between axonal branches depending on the distance from terminals.
复制标题
根据距末端的距离产生轴突分支之间微管差异的模型。
DOI：
10.1016/j.brainres.2022.148166
复制
发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Imanaka Chiaki,Shimada Satoshi,Ito Shino,Kamada Marina,Iguchi Tokuichi,Konishi Yoshiyuki
中科院分区：
文献类型：
--
作者：
河内美乃;太田麻友;豊田楓;中山実;浜千尋;曽根雅紀;Imanaka Chiaki,Shimada Satoshi,Ito Shino,Kamada Marina,Iguchi Tokuichi,Konishi Yoshiyuki
在轴突乔木的重塑过程中，分支的生长和收缩在单个轴突内受到差异调节。尽管细胞自主产生的微管（MT）周转差异被认为与选择性分支调节有关，但神经元在轴突分支之间产生MT差异的细胞系统尚未明确。由于相对于邻近的较短的分支，较长的分支中MT的周转往往较慢，因此认为涉及到依赖于分支长度的反馈调节。在本研究中，我们采用一个长度依赖的模型，在这个模型中，轴突末端分支的MT动力学参数是恒定的，从而建立了轴突末端分支的MT寿命模型。该模型预测邻近分支之间的MT寿命差异可能取决于与终端的距离。此外，还预测了以下几点。首先，整个乔木中MT的不稳定性降低了枝条间MT寿命的差异。其次，在MT进入分支点之前，MT的寿命就存在差异。在原代神经元轴突MT中，低浓度诺可达唑显著降低了MT转换指标小管蛋白的去酪氨酸（deTyr）和酪氨酸（Tyr）的差异。在分支点之前的轴突轴的扩展显微镜显示了MT上的deTyr/Tyr修饰的差异。我们的模型概括了分支之间MT转换的差异，并提供了依赖于轴突轴的几何形状的MT调节的反馈机制。
In the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry.