论文标题
在轴突初始段中对tau传输进行建模
Modeling tau transport in the axon initial segment
论文作者
论文摘要
通过假设tau蛋白可以在七个动力学状态下，我们开发了轴突和轴突初始段（AIS）中的tau蛋白转运模型。确定了两个单独的动力学常数，一个在轴突中，另一组在AIS中。这是通过将轴突中的模型预测与实验结果拟合，并通过将AIS中的模型预测与AIS中总tau浓度的线性增加拟合来完成。校准模型用于对轴突和AIS中的Tau传输进行预测。据我们所知，这是第一篇呈现AIS中Tau运输的数学模型的论文。我们的建模结果表明，自由tau与MTS的结合会在AIS中产生负tau的负梯度。这导致扩散驱动的tau从soma传输到AIS。该模型进一步表明，慢慢的轴突运输和tau的扩散驱动的转运在AIS中一起工作，从而移动tau。我们的数值结果预测了这两种机制之间的相互作用：随着与SOMA的距离的增加，扩散驱动的运输减小，而运动驱动的运输变得更大。因此，AIS中的机械用作泵，将tau移入轴突。
By assuming that tau protein can be in seven kinetic states, we developed a model of tau protein transport in the axon and in the axon initial segment (AIS). Two separate sets of kinetic constants were determined, one in the axon and the other in the AIS. This was done by fitting the model predictions in the axon with experimental results and by fitting the model predictions in the AIS with the assumed linear increase of the total tau concentration in the AIS. The calibrated model was used to make predictions about tau transport in the axon and in the AIS. To the best of our knowledge, this is the first paper that presents a mathematical model of tau transport in the AIS. Our modeling results suggest that binding of free tau to MTs creates a negative gradient of free tau in the AIS. This leads to diffusion-driven tau transport from the soma into the AIS. The model further suggests that slow axonal transport and diffusion-driven transport of tau work together in the AIS, moving tau anterogradely. Our numerical results predict an interplay between these two mechanisms: as the distance from the soma increases, the diffusion-driven transport decreases, while motor-driven transport becomes larger. Thus, the machinery in the AIS works as a pump, moving tau into the axon.
