Dynamic balance between vesicle transport and microtubule growth enables neurite outgrowth

Whole cell responses involve multiple subcellular processes (SCPs). To understand how balance between SCPs controls the dynamics of whole cell responses we studied neurite outgrowth in rat primary cortical neurons in culture. We used a combination of dynamical models and experiments to understand th...

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Bibliographic Details
Published in:PLoS computational biology 2019-05, Vol.15 (5), p.e1006877-e1006877
Main Authors: Yadaw, Arjun Singh, Siddiq, Mustafa M, Rabinovich, Vera, Tolentino, Rosa, Hansen, Jens, Iyengar, Ravi
Format: Article
Language:English
Subjects:
Ablation
Animals
Axonogenesis
Biological Transport - physiology
Biology
Biology and Life Sciences
Brain
Bulbs
Cell culture
Cell Physiological Phenomena
Cells, Cultured
Computer simulation
Exocytosis
Growth models
Mathematical models
Medicine
Microtubules
Microtubules - metabolism
Microtubules - physiology
Models, Neurological
Neural circuitry
Neurites - metabolism
Neurites - physiology
Neuronal Outgrowth - physiology
Neurons
Neurons - physiology
Neurosciences
Ordinary differential equations
Physiological aspects
Predictions
Protein Binding
Rats
siRNA
Stalling
Transport
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Summary:Whole cell responses involve multiple subcellular processes (SCPs). To understand how balance between SCPs controls the dynamics of whole cell responses we studied neurite outgrowth in rat primary cortical neurons in culture. We used a combination of dynamical models and experiments to understand the conditions that permitted growth at a specified velocity and when aberrant growth could lead to the formation of dystrophic bulbs. We hypothesized that dystrophic bulb formation is due to quantitative imbalances between SCPs. Simulations predict redundancies between lower level sibling SCPs within each type of high level SCP. In contrast, higher level SCPs, such as vesicle transport and exocytosis or microtubule growth characteristic of each type need to be strictly coordinated with each other and imbalances result in stalling of neurite outgrowth. From these simulations, we predicted the effect of changing the activities of SCPs involved in vesicle exocytosis or microtubule growth could lead to formation of dystrophic bulbs. siRNA ablation experiments verified these predictions. We conclude that whole cell dynamics requires balance between the higher-level SCPs involved and imbalances can terminate whole cell responses such as neurite outgrowth.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1006877