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Dendritic trafficking faces physiologically critical speed-precision tradeoffs

Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called th...

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Autores principales: Williams, Alex H, O'Donnell, Cian, Sejnowski, Terrence J, O'Leary, Timothy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201421/
https://www.ncbi.nlm.nih.gov/pubmed/28034367
http://dx.doi.org/10.7554/eLife.20556
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author Williams, Alex H
O'Donnell, Cian
Sejnowski, Terrence J
O'Leary, Timothy
author_facet Williams, Alex H
O'Donnell, Cian
Sejnowski, Terrence J
O'Leary, Timothy
author_sort Williams, Alex H
collection PubMed
description Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons. DOI: http://dx.doi.org/10.7554/eLife.20556.001
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spelling pubmed-52014212017-01-03 Dendritic trafficking faces physiologically critical speed-precision tradeoffs Williams, Alex H O'Donnell, Cian Sejnowski, Terrence J O'Leary, Timothy eLife Computational and Systems Biology Nervous system function requires intracellular transport of channels, receptors, mRNAs, and other cargo throughout complex neuronal morphologies. Local signals such as synaptic input can regulate cargo trafficking, motivating the leading conceptual model of neuron-wide transport, sometimes called the ‘sushi-belt model’ (Doyle and Kiebler, 2011). Current theories and experiments are based on this model, yet its predictions are not rigorously understood. We formalized the sushi belt model mathematically, and show that it can achieve arbitrarily complex spatial distributions of cargo in reconstructed morphologies. However, the model also predicts an unavoidable, morphology dependent tradeoff between speed, precision and metabolic efficiency of cargo transport. With experimental estimates of trafficking kinetics, the model predicts delays of many hours or days for modestly accurate and efficient cargo delivery throughout a dendritic tree. These findings challenge current understanding of the efficacy of nucleus-to-synapse trafficking and may explain the prevalence of local biosynthesis in neurons. DOI: http://dx.doi.org/10.7554/eLife.20556.001 eLife Sciences Publications, Ltd 2016-12-30 /pmc/articles/PMC5201421/ /pubmed/28034367 http://dx.doi.org/10.7554/eLife.20556 Text en © 2016, Williams et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Williams, Alex H
O'Donnell, Cian
Sejnowski, Terrence J
O'Leary, Timothy
Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title_full Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title_fullStr Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title_full_unstemmed Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title_short Dendritic trafficking faces physiologically critical speed-precision tradeoffs
title_sort dendritic trafficking faces physiologically critical speed-precision tradeoffs
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5201421/
https://www.ncbi.nlm.nih.gov/pubmed/28034367
http://dx.doi.org/10.7554/eLife.20556
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