Cargo distribution within eukaryotic cells relies on the active transport mechanisms driven by molecular motors. Despite their critical role, the intricate relationship between motor transport properties and cargo binding - and its impact on motor distribution - remains inadequately understood. Additionally, improper regulation of ubiquitination, a pivotal post-translational modification that affects protein degradation, activation, and localization, is associated with several neurodegenerative diseases. Recent data showed that ubiquitination can alter motor-cargo binding of the Kinesin-3 motor UNC-104 / KIF1A that transports synaptic vesicles. To investigate how ubiquitin-like modifications affect motor protein function, particularly cargo binding, transport properties, and distribution, we utilize the PLM neuron of C. elegans as a model system. Using fluorescent microscopy, we assess the distribution of cargo-bound UNC-104 motors along the axon and probe their dynamics using FRAP experiments. We model cargo binding kinetics with a Master equation and motor density dynamics using a Fokker-Planck approach. Our combined experimental and theoretical analysis reveals that ubiquitin-like knockdowns enhance UNC-104's cooperative binding to its cargo. However, these modifications do not affect UNC-104's transport properties, such as processivity and diffusivity. Thus, while ubiquitin-like modifications significantly impact the cargo-binding of UNC-104, they do not alter its transport dynamics, keeping the homeostatic distribution of UNC-104 unchanged.
A hopping mechanism for cargo transport by molecular motors in crowded microtubules
大多数设计用于研究由分子马达驱动的货物双向运动的模型都依赖于这样一种想法，即如果将不同极性的马达安排到马达-货物复合体中以执行必要的工作，则可以通过外部代理来协调马达[gross 04]。虽然这些模型为我们提供了重要的见解，这些现象，仍然有许多未回答的问题，通过复杂的运动发生在拥挤的微管的机制。例如（i）货物结合如何影响运动运动？与此相关-（ii）微管上其他马达（以及其他货物）的存在如何影响马达-货物复合物的运动性？我们从不同的角度讨论这些问题。货物的运动在这里被认为是一个跳跃的过程，由相邻的马达之间的货物转移。有鉴于此，我们研究的条件下，货物可能会显示双向运动，即使是由一个单一的极性电机。通过将相互作用的电动机和货物的集合的动力学映射到一个不对称的简单排斥过程（ASEP）中，可以使用Derrida [Derrida et al]引入的矩阵分析来解决该模型在长时间区域中的全局特性。
驱动蛋白是一种沿微管运输货物的分子马达。动力学模型\cite{Clancy11}描述了许多关于驱动蛋白-1的{ \it in vitro}实验的结果，其中一个转变对应于拴系的运动头的向前运动和随后的结合。我们认为，在一个粘弹性介质中，如细胞的胞质溶胶，这一步是不马尔可夫的，必须描述一个非指数的等待时间分布。我们引入一个半马尔可夫动力学模型驱动蛋白，考虑到这种效果。对于任意的等待时间分布，我们计算所做的步数的矩母函数，并由此确定电机的平均速度和扩散常数。我们说明了我们的结果的情况下，等待时间分布是威布尔。我们发现，对于现实的参数值，粘弹性降低的速度和扩散常数，但增加的随机性（或范诺因子）。
