A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks

  1. Danielle Holz
  2. Aaron R Hall
  3. Eiji Usukura
  4. Sawako Yamashiro
  5. Naoki Watanabe
  6. Dimitrios Vavylonis  Is a corresponding author
  1. Lehigh University, United States
  2. Kyoto University, Japan

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

The following data sets were generated

Article and author information

Author details

  1. Danielle Holz

    Department of Physics, Lehigh University, Bethlehem, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Aaron R Hall

    Department of Physics, Lehigh University, Bethlehem, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eiji Usukura

    Laboratory of Single-Molecule Cell Biology, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Sawako Yamashiro

    Laboratory of Single-Molecule Cell Biology, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Naoki Watanabe

    Laboratory of Single-Molecule Cell Biology, Kyoto University, Kyoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Dimitrios Vavylonis

    Department of Physics, Lehigh University, Bethlehem, United States
    For correspondence
    vavylonis@lehigh.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1802-3262

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.

Reviewing Editor

  1. Alphee Michelot, Institut de Biologie du Développement, France

Version history

  1. Received: April 1, 2021
  2. Preprint posted: April 2, 2021 (view preprint)
  3. Accepted: June 4, 2022
  4. Accepted Manuscript published: June 7, 2022 (version 1)
  5. Accepted Manuscript updated: June 9, 2022 (version 2)
  6. Version of Record published: July 4, 2022 (version 3)

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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  1. Danielle Holz
  2. Aaron R Hall
  3. Eiji Usukura
  4. Sawako Yamashiro
  5. Naoki Watanabe
  6. Dimitrios Vavylonis
(2022)
A mechanism with severing near barbed ends and annealing explains structure and dynamics of dendritic actin networks
eLife 11:e69031.
https://doi.org/10.7554/eLife.69031

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https://doi.org/10.7554/eLife.69031