Friday, November 13, 201510:00 AM - 11:00 AMCNLS Conference Room (TA-3, Bldg 1690)|
A mathematical model of microtubular transport reveals tradeoffs in speed and precision in complex neuronal morphologies
Alex WilliamsStanford University
A typical neuron displays stunningly complex morphology, with long, extended processes. To support their basic biological functions, neurons must control the spatial distribution of organelles and macromolecules throughout their dendritic arbors. Yet, it remains unclear how this is accomplished. Previous work suggests that localized biochemical signals influence the trafficking, delivery and expression of molecular cargo along microtubules. However, it is unknown whether patterned spatial expression of molecular cargo can arise from a decentralized transport system built from purely local mechanisms. We mathematically formalized a previously proposed “sushi belt” model of microtubule transport (Doyle and Kiebler, 2011) and showed that arbitrarily complex spatial distributions of cargo can be achieved by localized mechanisms. However, this model predicts an unavoidable tradeoff between speed and precision of cargo delivery that can be tested experimentally. Reliable cargo delivery required that cargo transport along microtubules occur on a faster timescale than cargo dissociation from the microtubules. Increasing the cargo dissociation rate provided faster transport, but required complex, global re-tuning of the trafficking rates to maintain precision. Additionally, these solutions tended to be fragile in the sense that small changes in the target distribution led to large changes in the optimal delivery strategy. Together, these results suggest that macromolecules with stereotyped expression patterns might be tuned for fast and precise transport, but cargoes requiring plastic expression patterns face a tradeoff in the speed and precision of transport.
Host: Misha Chertkov