A mechanism with severing near barbed ends andannealing explains structure and dynamics of dendriticactin networks
Abstract
Single molecule imaging has shown that part of actin disassembles within a few seconds after incorporation into the dendritic filament network in lamellipodia, suggestive of frequent destabilization near barbed ends. To investigate the mechanisms behind network remodeling, we created a stochastic model with polymerization, depolymerization, branching, capping, uncapping, severing, oligomer diffusion, annealing, and debranching. We find that filament severing, enhanced near barbed ends, can explain the single molecule actin lifetime distribution, if oligomer fragments reanneal to free ends with rate constants comparable to in vitro measurements. The same mechanism leads to actin networks consistent with measured filament, end, and branch concentrations. These networks undergo structural remodeling, leading to longer filaments away from the leading edge, at the +/- 35𝑜 orientation pattern. Imaging of actin speckle lifetimes at sub-second resolution verifies frequent disassembly of newly-assembled actin. We thus propose a unified mechanism that fits a diverse set of basic lamellipodia phenomenology.
Data availability
All data reported in this project are present within the published figures and Supplemental Information. The code for simulations is available at https://github.com/vavylonis/LamellipodiumSeverAnnealand will allow for all simulation plots to be reproduced. The experimental SiMS data of Figure 6 and Figure 6-supplement 1 have been provided as excel files containing the speckle tracks using the SpeckleTrackerJ ImageJ plugin
Article and author information
Author details
Funding
National Institutes of Health (R35GM136372)
- Danielle Holz
- Aaron R Hall
- Eiji Usukura
- Sawako Yamashiro
- Naoki Watanabe
- Dimitrios Vavylonis
National Institutes of Health (R01GM114201)
- Danielle Holz
- Aaron R Hall
- Dimitrios Vavylonis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Holz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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