Dendritic trafficking faces fundamental 1 speed - precision tradeoffs

12 Most neurons have complex morphologies with long processes and dynamic, nonuniform spatial expression patterns of subcellular organelles and macromolecules. It is thought that trafficking and delivery of this subcellular cargo depends on purely local signals, rather than a global addressing system. Yet it remains unclear how such a decentralized system performs in complex morphologies. We mathematically formalize a previously proposed “sushi belt” model of microtubule transport (Doyle and Kiebler, 2011) and show how arbitrarily complex spatial distributions of cargo can be achieved by local signaling mechanisms. We reveal that this model predicts an unavoidable and physiologically critical tradeoff between speed and precision of cargo delivery that can be tested experimentally. More sophisticated variants of the sushi belt model can provide both fast and precise transport; however, these require global tuning of trafficking kinetics, and their performance is fragile to changes in the required spatial distribution of cargo. 13