Real-Time Tracking of Vesicles in Living Cells Reveals That Tau-Hyperphosphorylation Suppresses Unidirectional Transport by Motor Proteinsopen access
- Authors
- Lee, Eunsang; Kim, Donghee; Song, Yo Han; Shin, Kyujin; Song, Sanggeun; Lee, Minho; Goh, Yeongchang; Lim, Mi Hee; Kim, Ji-Hyun; Sung, Jaeyoung; Lee, Kang Taek
- Issue Date
- May-2024
- Publisher
- American Chemical Society
- Keywords
- microtubule; motor protein; tau aggregation; transport dynamics; upconverting nanoparticle
- Citation
- Chemical and Biomedical Imaging, v.2, no.5, pp 362 - 373
- Pages
- 12
- Journal Title
- Chemical and Biomedical Imaging
- Volume
- 2
- Number
- 5
- Start Page
- 362
- End Page
- 373
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/73854
- DOI
- 10.1021/cbmi.4c00016
- ISSN
- 2832-3637
- Abstract
- Synaptic vesicle transport by motor proteins along microtubules is a crucially 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 the transport dynamics of motor proteins on the microtubule remains unknown. Here, we discover that the 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 those of 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 fast vesicle-transport along the microtubule can be a mechanism of neurodegenerative disorders associated with tau-hyperphosphorylation. © 2024 The Authors. Co-published by Nanjing University and American Chemical Society
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Collections - College of Natural Sciences > Department of Chemistry > 1. Journal Articles
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