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Dendritic trafficking faces physiologically critical speed-precision tradeoffs

Published version
Peer-reviewed

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Authors

Williams, AH 
O Donnell, C 
Sejnowski, TJ 
O Leary, T 

Abstract

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.

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Keywords

regulation, active transport, plasticity, tagging hypothesis, morphology, motor proteins

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

5

Publisher

eLife
Sponsorship
This research was supported by the Department of Energy Computational Science Graduate Fellowship, NIH Grant 1P01NS079419, NIH Grant P41GM103712, the Howard Hughes Medical Institute.