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A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics

Neurofilaments(NFs) are the most abundant intermediate filaments that make up the inner volume of axon, with possible phosphorylation on their side arms, and their slow axonal transport by molecular motors along microtubule tracks in a “stop-and-go” manner with rapid, intermittent and bidirectional...

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Autores principales: Jia, Zelin, Li, Yinyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954336/
https://www.ncbi.nlm.nih.gov/pubmed/33711034
http://dx.doi.org/10.1371/journal.pone.0247656
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author Jia, Zelin
Li, Yinyun
author_facet Jia, Zelin
Li, Yinyun
author_sort Jia, Zelin
collection PubMed
description Neurofilaments(NFs) are the most abundant intermediate filaments that make up the inner volume of axon, with possible phosphorylation on their side arms, and their slow axonal transport by molecular motors along microtubule tracks in a “stop-and-go” manner with rapid, intermittent and bidirectional motion. The kinetics of NFs and morphology of axon are dramatically different between myelinate internode and unmyelinated node of Ranvier. The NFs in the node transport as 7.6 times faster as in the internode, and the distribution of NFs population in the internode is 7.6 folds as much as in the node of Ranvier. We hypothesize that the phosphorylation of NFs could reduce the on-track rate and slow down their transport velocity in the internode. By modifying the ‘6-state’ model with (a) an extra phosphorylation kinetics to each six state and (b) construction a new ‘8-state’ model in which NFs at off-track can be phosphorylated and have smaller on-track rate, our model and simulation demonstrate that the phosphorylation-induced decrease of on-track rate could slow down the NFs average velocity and increase the axonal caliber. The degree of phosphorylation may indicate the extent of velocity reduction. The Continuity equation used in our paper predicts that the ratio of NFs population is inverse proportional to the ratios of average velocity of NFs between node of Ranvier and internode. We speculate that the myelination of axon could increase the level of phosphorylation of NF side arms, and decrease the possibility of NFs to get on-track of microtubules, therefore slow down their transport velocity. In summary, our work provides a potential mechanism for understanding the phosphorylation kinetics of NFs in regulating their transport and morphology of axon in myelinated axons, and the different kinetics of NFs between node and internode.
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spelling pubmed-79543362021-03-22 A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics Jia, Zelin Li, Yinyun PLoS One Research Article Neurofilaments(NFs) are the most abundant intermediate filaments that make up the inner volume of axon, with possible phosphorylation on their side arms, and their slow axonal transport by molecular motors along microtubule tracks in a “stop-and-go” manner with rapid, intermittent and bidirectional motion. The kinetics of NFs and morphology of axon are dramatically different between myelinate internode and unmyelinated node of Ranvier. The NFs in the node transport as 7.6 times faster as in the internode, and the distribution of NFs population in the internode is 7.6 folds as much as in the node of Ranvier. We hypothesize that the phosphorylation of NFs could reduce the on-track rate and slow down their transport velocity in the internode. By modifying the ‘6-state’ model with (a) an extra phosphorylation kinetics to each six state and (b) construction a new ‘8-state’ model in which NFs at off-track can be phosphorylated and have smaller on-track rate, our model and simulation demonstrate that the phosphorylation-induced decrease of on-track rate could slow down the NFs average velocity and increase the axonal caliber. The degree of phosphorylation may indicate the extent of velocity reduction. The Continuity equation used in our paper predicts that the ratio of NFs population is inverse proportional to the ratios of average velocity of NFs between node of Ranvier and internode. We speculate that the myelination of axon could increase the level of phosphorylation of NF side arms, and decrease the possibility of NFs to get on-track of microtubules, therefore slow down their transport velocity. In summary, our work provides a potential mechanism for understanding the phosphorylation kinetics of NFs in regulating their transport and morphology of axon in myelinated axons, and the different kinetics of NFs between node and internode. Public Library of Science 2021-03-12 /pmc/articles/PMC7954336/ /pubmed/33711034 http://dx.doi.org/10.1371/journal.pone.0247656 Text en © 2021 Jia, Li http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jia, Zelin
Li, Yinyun
A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title_full A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title_fullStr A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title_full_unstemmed A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title_short A possible mechanism for neurofilament slowing down in myelinated axon: Phosphorylation-induced variation of NF kinetics
title_sort possible mechanism for neurofilament slowing down in myelinated axon: phosphorylation-induced variation of nf kinetics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954336/
https://www.ncbi.nlm.nih.gov/pubmed/33711034
http://dx.doi.org/10.1371/journal.pone.0247656
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