dc.contributor.authorKoon, Yen Ling
dc.contributor.authorKoh, Cheng Gee
dc.contributor.authorChiam, Keng-Hwee
dc.contributor.editorYang, Yanmin*
dc.date.accessioned2014-06-04T06:36:04Z
dc.date.available2014-06-04T06:36:04Z
dc.date.copyright2014en_US
dc.date.issued2014
dc.identifier.citationKoon, 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-.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10220/19568
dc.description.abstractIntracellular 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.en_US
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)
dc.language.isoenen_US
dc.relation.ispartofseriesPLoS ONEen_US
dc.rights© 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.en_US
dc.subjectDRNTU::Science::Biological sciences::Biophysics
dc.titleComputational modeling reveals optimal strategy for kinase transport by microtubules to nerve terminalsen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0092437
dc.description.versionPublished versionen_US


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