标题： UNC-104 的运输特性是稳健的，且不依赖于其货物结合的变化 显示英文标题

标题： UNC-104 transport properties are robust and independent of changes in its cargo binding

摘要： 真核细胞内货物的分布依赖于由分子马达驱动的主动运输机制。 尽管它们起着关键作用，但马达运输特性与货物结合之间的复杂关系及其对马达分布的影响仍了解不足。 此外，泛素化不适当的调控，这是一种影响蛋白质降解、激活和定位的关键翻译后修饰，与几种神经退行性疾病有关。 最近的数据表明，泛素化可以改变Kinesin-3马达UNC-104/KIF1A与运输突触小泡的货物结合。 为了研究泛素样修饰如何影响马达蛋白功能，特别是货物结合、运输特性和分布，我们利用秀丽线虫的PLM神经元作为模型系统。 使用荧光显微镜，我们评估轴突上与货物结合的UNC-104马达的分布，并通过FRAP实验探测其动态特性。 我们用主方程模拟货物结合动力学，并用福克-普朗克方法模拟马达密度动力学。 我们的实验和理论分析结果表明，泛素样抑制增强了UNC-104与其货物的协同结合。 然而，这些修饰不影响UNC-104的运输特性，如过程性和扩散性。 因此，虽然泛素样修饰显著影响UNC-104的货物结合，但不会改变其运输动力学，保持UNC-104的稳态分布不变。 显示英文摘要

摘要： 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.