Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells
Abstract
Synaptic vesicle transport by motor proteins along microtubules is a crucial active process underlying neuronal communication. It is known that microtubules are destabilized by tau-hyperphosphorylation, which causes tau proteins to detach from microtubules and form neurofibril tangles. However, how tau-phosphorylation affects transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that long-distance unidirectional motion of vesicle-motor protein multiplexes (VMPMs) in living cells is suppressed under tau-hyperphosphorylation, with the consequent loss of fast vesicle-transport along the microtubule. The VMPMs in hyperphosphorylated cells exhibit seemingly bidirectional random motion, with dynamic properties far different from VMPM motion in normal cells. We establish a parsimonious physicochemical model of VMPM's active motion that provides a unified, quantitative explanation and predictions for our experimental results. Our analysis reveals that, under hyperphosphorylation conditions, motor-protein-multiplexes have both static and dynamic motility fluctuations. The loss of the fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation.
Keywords
Cite
@article{arxiv.2401.15413,
title = {Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells},
author = {Eunsang Lee and Donghee Kim and Yo Han Song and Kyujin Shin and Sanggeun Song and Minho Lee and Yeongchang Goh and Mi Hee Lim and Ji-Hyun Kim and Jaeyoung Sung and Kang Taek Lee},
journal= {arXiv preprint arXiv:2401.15413},
year = {2024}
}