Transport properties of the motor protein UNC-104 are robust and independent of changes in its cargo binding.

Abstract

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.