Department of Biological Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai 400 005, India.
The Institute of Mathematical Sciences, CIT Campus, Taramani, Chennai 600 113, India.
J Cell Sci. 2023 Jun 15;136(12). doi: 10.1242/jcs.261223. Epub 2023 Jun 21.
Stationary clusters of vesicles are a prominent feature of axonal transport, but little is known about their physiological and functional relevance to axonal transport. Here, we investigated the role of vesicle motility characteristics in modulating the formation and lifetimes of such stationary clusters, and their effect on cargo flow. We developed a simulation model describing key features of axonal cargo transport, benchmarking the model against experiments in the posterior lateral mechanosensory neurons of Caenorhabditis elegans. Our simulations included multiple microtubule tracks and varied cargo motion states, and account for dynamic cargo-cargo interactions. Our model also incorporates static obstacles to vesicle transport in the form of microtubule ends, stalled vesicles and stationary mitochondria. We demonstrate, both in simulations and in an experimental system, that a reduction in reversal rates is associated with a higher proportion of long-lived stationary vesicle clusters and reduced net anterograde transport. Our simulations support the view that stationary clusters function as dynamic reservoirs of cargo vesicles, and reversals aid cargo in navigating obstacles and regulate cargo transport by modulating the proportion of stationary vesicle clusters along the neuronal process.
静止的囊泡簇是轴突运输的一个显著特征，但人们对其与轴突运输的生理和功能相关性知之甚少。在这里，我们研究了囊泡运动特征在调节这种静止簇的形成和寿命及其对货物流动的影响中的作用。我们开发了一个模拟模型，描述了轴突货物运输的关键特征，该模型通过对秀丽隐杆线虫后外侧机械感觉神经元中的实验进行了基准测试。我们的模拟包括多个微管轨道和不同的货物运动状态，并考虑了动态货物-货物相互作用。我们的模型还以微管末端、停滞的囊泡和静止的线粒体的形式纳入了对囊泡运输的静态障碍物。我们在模拟和实验系统中都证明，反转率的降低与长寿命静止囊泡簇的比例增加和正向运输减少有关。我们的模拟支持这样一种观点，即静止簇作为货物囊泡的动态储库发挥作用，反转有助于货物在障碍物中导航，并通过调节神经元过程中静止囊泡簇的比例来调节货物运输。
