Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals
Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational mode...
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sg-ntu-dr.10356-1042002023-02-28T17:06:12Z Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals Koon, Yen Ling Koh, Cheng Gee Chiam, Keng-Hwee Yang, Yanmin School of Biological Sciences DRNTU::Science::Biological sciences::Biophysics Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase) transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2014-06-04T06:36:04Z 2019-12-06T21:28:22Z 2014-06-04T06:36:04Z 2019-12-06T21:28:22Z 2014 2014 Journal Article Koon, Y. L., Koh, C. G., & Chiam, K.-H. (2014). Computational Modeling Reveals Optimal Strategy for Kinase Transport by Microtubules to Nerve Terminals. PLoS ONE, 9(4), e92437-. 1932-6203 https://hdl.handle.net/10356/104200 http://hdl.handle.net/10220/19568 10.1371/journal.pone.0092437 24691408 en PLoS ONE © 2014 Koon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf |
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DRNTU::Science::Biological sciences::Biophysics Koon, Yen Ling Koh, Cheng Gee Chiam, Keng-Hwee Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
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Intracellular transport of proteins by motors along cytoskeletal filaments is crucial to the proper functioning of many eukaryotic cells. Since most proteins are synthesized at the cell body, mechanisms are required to deliver them to the growing periphery. In this article, we use computational modeling to study the strategies of protein transport in the context of JNK (c-JUN NH2-terminal kinase) transport along microtubules to the terminals of neuronal cells. One such strategy for protein transport is for the proteins of the JNK signaling cascade to bind to scaffolds, and to have the whole protein-scaffold cargo transported by kinesin motors along microtubules. We show how this strategy outperforms protein transport by diffusion alone, using metrics such as signaling rate and signal amplification. We find that there exists a range of scaffold concentrations for which JNK transport is optimal. Increase in scaffold concentration increases signaling rate and signal amplification but an excess of scaffolds results in the dilution of reactants. Similarly, there exists a range of kinesin motor speeds for which JNK transport is optimal. Signaling rate and signal amplification increases with kinesin motor speed until the speed of motor translocation becomes faster than kinase/scaffold-motor binding. Finally, we suggest experiments that can be performed to validate whether, in physiological conditions, neuronal cells do indeed adopt such an optimal strategy. Understanding cytoskeletal-assisted protein transport is crucial since axonal and cell body accumulation of organelles and proteins is a histological feature in many human neurodegenerative diseases. In this paper, we have shown that axonal transport performance changes with altered transport component concentrations and transport speeds wherein these aspects can be modulated to improve axonal efficiency and prevent or slowdown axonal deterioration. |
author2 |
Yang, Yanmin |
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Yang, Yanmin Koon, Yen Ling Koh, Cheng Gee Chiam, Keng-Hwee |
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Article |
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Koon, Yen Ling Koh, Cheng Gee Chiam, Keng-Hwee |
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Koon, Yen Ling |
title |
Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
title_short |
Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
title_full |
Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
title_fullStr |
Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
title_full_unstemmed |
Computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
title_sort |
computational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminals |
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2014 |
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https://hdl.handle.net/10356/104200 http://hdl.handle.net/10220/19568 |
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1759858259579109376 |