Real-Time Tracking of Vesicles in Living Cells Reveals That Tau-Hyperphosphorylation Suppresses Unidirectional Transport by Motor Proteins

• DOI: 10.1021/cbmi.4c00016
• Publication Date: 2024-04-23T09:24:24Z
• Authors: Eunsang Lee; Donghee Kim; Yo Han Song; Kyujin Shin; Sanggeun Song; Minho Lee; Yeongchang Goh; Mi Hee Lim; Ji-Hyun Kim; Jaeyoung Sung; Kang Taek Lee
• Keywords: Hyperphosphorylation; Molecular motor; Axoplasmic transport; Kinesin; Tau protein; Vesicular Transport Proteins; Cyclin-dependent kinase 5

Synaptic vesicle transport by motor proteins along microtubules is a crucially active process underlying neuronal communication. It known that are destabilized tau-hyperphosphorylation, which causes tau to detach from and form neurofibril tangles. However, how tau-phosphorylation affects the dynamics of on microtubule remains unknown. Here, we discover long-distance unidirectional motion vesicle-motor protein multiplexes (VMPMs) in living cells suppressed under with consequent loss fast vesicle-transport microtubule. The VMPMs hyperphosphorylated exhibit seemingly bidirectional random motion, dynamic properties far different those VMPM normal cells. We establish parsimonious physicochemical model VMPM's provides unified, quantitative explanation predictions for our experimental results. Our analysis reveals that, hyperphosphorylation conditions, have both static motility fluctuations. can be mechanism neurodegenerative disorders associated tau-hyperphosphorylation.