Shee Amir, Sabharwal Vidur, Koushika Sandhya P, Nandi Amitabha, Chaudhuri Debasish
Northwestern University, Northwestern Institute on Complex Systems and ESAM, Evanston, Illinois 60208, USA.
Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005, Odisha, India.
Phys Rev E. 2025 Jun;111(6-1):064404. doi: 10.1103/PhysRevE.111.064404.
Cargo distribution in eukaryotic cells relies on active transport by molecular motors. Despite its importance, the relationship between motor transport properties and cargo binding remains inadequately understood. Moreover, improper regulation of ubiquitination, a key post-translational modification affecting protein degradation, activation, and localization, is linked to several neurodegenerative diseases. To investigate how ubiquitin-like modifications influence motor function, we use the PLM neuron of C. elegans as a model system. Through fluorescent microscopy, we examine the distribution of cargo-bound UNC-104 along the axon and probe its dynamics with FRAP experiments. We model cargo binding kinetics using a master equation and motor density dynamics via the Fokker-Planck approach. Our previous analysis showed that ubiquitin-like knockdowns enhance UNC-104's cooperative binding to cargo, but our combined experimental and theoretical analysis here demonstrates that they do not impact its transport properties, such as processivity and diffusivity. Thus, while these modifications significantly impact UNC-104's cargo binding, they do not alter its dynamics, maintaining the homeostatic distribution of motors.
真核细胞中的货物运输依赖于分子马达的主动运输。尽管其很重要，但马达运输特性与货物结合之间的关系仍未得到充分理解。此外，泛素化是一种影响蛋白质降解、激活和定位的关键翻译后修饰，其调控不当与多种神经退行性疾病有关。为了研究类泛素修饰如何影响马达功能，我们使用秀丽隐杆线虫的PLM神经元作为模型系统。通过荧光显微镜，我们检查了沿轴突的货物结合型UNC-104的分布，并通过光漂白后荧光恢复实验探测其动力学。我们使用主方程对货物结合动力学进行建模，并通过福克-普朗克方法对马达密度动力学进行建模。我们之前的分析表明，类泛素敲低增强了UNC-104与货物的协同结合，但我们在此处结合实验和理论的分析表明，它们不会影响其运输特性，如持续性和扩散性。因此，虽然这些修饰显著影响UNC-104与货物的结合，但它们不会改变其动力学，从而维持马达的稳态分布。
