Kuznetsov I A, Kuznetsov A V
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Math Phys Eng Sci. 2019 Aug;475(2228):20190284. doi: 10.1098/rspa.2019.0284. Epub 2019 Aug 28.
A model simulating the transport of dense core vesicles (DCVs) in type II axonal terminals of motoneurons has been developed. The morphology of type II terminals is characterized by the large number of boutons. The lack of both scaled-up DCV transport and scaled-down DCV capture in boutons results in a less efficient supply of DCVs to distal boutons. Furthermore, the large number of boutons that DCVs pass as they move anterogradely until they reach the most distal bouton may lead to the capture of a majority of DCVs before they turn around in the most distal bouton to move in the retrograde direction. This may lead to a reduced retrograde flux of DCVs and a lack of DCV circulation in type II terminals. The developed model simulates DCV concentrations in boutons, DCV fluxes between the boutons, age density distributions of DCVs and the mean age of DCVs in various boutons. Unlike published experimental observations, our model predicts DCV circulation in type II terminals after these terminals are filled to saturation. This disagreement is likely because experimentally observed terminals were not at steady state, but rather were accumulating DCVs for later release. Our estimates show that the number of DCVs in the transiting state is much smaller than that in the resident state. DCVs travelling in the axon, rather than DCVs transiting in the terminal, may provide a reserve of DCVs for replenishing boutons after a release. The techniques for modelling transport of DCVs developed in our paper can be used to model the transport of other organelles in axons.
已开发出一种模拟运动神经元II型轴突终末中致密核心囊泡（DCV）运输的模型。II型终末的形态特征是有大量的终扣。终扣中缺乏按比例放大的DCV运输和按比例缩小的DCV捕获，导致向远端终扣供应DCV的效率较低。此外，DCV在向最远端终扣顺行移动过程中会经过大量终扣，这可能导致大多数DCV在到达最远端终扣并转向逆行方向之前就被捕获。这可能导致II型终末中DCV的逆行通量减少以及DCV循环缺乏。所开发的模型模拟了终扣中的DCV浓度、终扣之间的DCV通量、DCV的年龄密度分布以及各个终扣中DCV的平均年龄。与已发表的实验观察结果不同，我们的模型预测在II型终末充满至饱和后会出现DCV循环。这种不一致可能是因为实验观察到的终末并非处于稳态，而是在积累DCV以便后续释放。我们的估计表明，处于转运状态的DCV数量远小于处于驻留状态的DCV数量。在轴突中移动的DCV，而非在终末中转的DCV，可能为释放后补充终扣提供DCV储备。我们论文中开发的DCV运输建模技术可用于模拟轴突中其他细胞器的运输。
