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/2016/02/07/037374.abstract
AB Neuronal function depends on the appropriate subcellular distribution of channels, receptors, mRNAs, and other components. Trafficking of subcellular cargo to specific locations is regulated by local signals such as synaptic input, yet it remains unclear how such a decentralized system performs in complex morphologies. We mathematically formalize a popular, conceptual model of microtubule transport (the “sushi-belt model”, Doyle and Kiebler, 2011), and show that it can achieve arbitrarily complex spatial distributions of cargo in realistic morphologies. However, we reveal that this model predicts a critical tradeoff between the speed and precision of cargo delivery; given experimental estimates of trafficking kinetics the model predicts delays of many hours for modestly accurate cargo distribution. We explore the possibility that biological mechanisms might have more sophisticated, globally fine-tuned trafficking kinetics to enable both fast and precise transport; however, tuned mechanisms are less flexible, and are fragile to changes in spatial demand for cargo.