Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells
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arXiv
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| Autores principales: | , , , , , , , , , , |
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| Formato: | Preprint |
| Publicado: |
2024
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| _version_ | 1866917647879241728 |
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| author | 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 |
| author_facet | 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 |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2401_15413 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells 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 Biological Physics 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. |
| title | Hyperphosphorylation-Induced Phase Transition in Vesicle Delivery Dynamics of Motor Proteins in Neuronal Cells |
| topic | Biological Physics |
| url | https://arxiv.org/abs/2401.15413 |