RT Journal Article
SR Electronic
T1 Dendritic trafficking faces physiologically critical speed-precision tradeoffs
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 037374
DO 10.1101/037374
A1 Alex H. Williams
A1 Cian O’Donnell
A1 Terrence Sejnowski
A1 Timothy O’Leary
YR 2016
UL http://biorxiv.org/content/early/2016/08/11/037374.abstract
AB 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, showing how 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.