---
_id: '9414'
abstract:
- lang: eng
  text: Microtubule plus-end depolymerization rate is a potentially important target
    of physiological regulation, but it has been challenging to measure, so its role
    in spatial organization is poorly understood. Here we apply a method for tracking
    plus ends based on time difference imaging to measure depolymerization rates in
    large interphase asters growing in Xenopus egg extract. We observed strong spatial
    regulation of depolymerization rates, which were higher in the aster interior
    compared with the periphery, and much less regulation of polymerization or catastrophe
    rates. We interpret these data in terms of a limiting component model, where aster
    growth results in lower levels of soluble tubulin and microtubule-associated proteins
    (MAPs) in the interior cytosol compared with that at the periphery. The steady-state
    polymer fraction of tubulin was ∼30%, so tubulin is not strongly depleted in the
    aster interior. We propose that the limiting component for microtubule assembly
    is a MAP that inhibits depolymerization, and that egg asters are tuned to low
    microtubule density.
acknowledgement: The authors thank the members of Mitchison, Brugués, and Jay Gatlin
  groups (University of Wyoming) for discussions. We thank Heino Andreas (MPI-CBG)
  for frog maintenance. We thank Nikon for microscopy support at Marine Biological
  Laboratory (MBL). K.I. was supported by fellowships from the Honjo International
  Scholarship Foundation and Center of Systems Biology Dresden. F.D. was supported
  by the DIGGS-BB fellowship provided by the German Research Foundation (DFG). P.C.
  is supported by a Boehringer Ingelheim Fonds PhD fellowship. J.F.P. was supported
  by a fellowship from the Fannie and John Hertz Foundation. M.L.’s research is supported
  by European Research Council (ERC) Grant no. ERC-2015-StG-679239. J.B.’s research
  is supported by the Human Frontiers Science Program (CDA00074/2014). T.J.M.’s research
  is supported by National Institutes of Health Grant no. R35GM131753.
article_processing_charge: No
article_type: original
author:
- first_name: Keisuke
  full_name: Ishihara, Keisuke
  last_name: Ishihara
- first_name: Franziska
  full_name: Decker, Franziska
  last_name: Decker
- first_name: Paulo R
  full_name: Dos Santos Caldas, Paulo R
  id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87
  last_name: Dos Santos Caldas
  orcid: 0000-0001-6730-4461
- first_name: James F.
  full_name: Pelletier, James F.
  last_name: Pelletier
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
- first_name: Jan
  full_name: Brugués, Jan
  last_name: Brugués
- first_name: Timothy J.
  full_name: Mitchison, Timothy J.
  last_name: Mitchison
citation:
  ama: Ishihara K, Decker F, Dos Santos Caldas PR, et al. Spatial variation of microtubule
    depolymerization in large asters. <i>Molecular Biology of the Cell</i>. 2021;32(9):869-879.
    doi:<a href="https://doi.org/10.1091/MBC.E20-11-0723">10.1091/MBC.E20-11-0723</a>
  apa: Ishihara, K., Decker, F., Dos Santos Caldas, P. R., Pelletier, J. F., Loose,
    M., Brugués, J., &#38; Mitchison, T. J. (2021). Spatial variation of microtubule
    depolymerization in large asters. <i>Molecular Biology of the Cell</i>. American
    Society for Cell Biology. <a href="https://doi.org/10.1091/MBC.E20-11-0723">https://doi.org/10.1091/MBC.E20-11-0723</a>
  chicago: Ishihara, Keisuke, Franziska Decker, Paulo R Dos Santos Caldas, James F.
    Pelletier, Martin Loose, Jan Brugués, and Timothy J. Mitchison. “Spatial Variation
    of Microtubule Depolymerization in Large Asters.” <i>Molecular Biology of the
    Cell</i>. American Society for Cell Biology, 2021. <a href="https://doi.org/10.1091/MBC.E20-11-0723">https://doi.org/10.1091/MBC.E20-11-0723</a>.
  ieee: K. Ishihara <i>et al.</i>, “Spatial variation of microtubule depolymerization
    in large asters,” <i>Molecular Biology of the Cell</i>, vol. 32, no. 9. American
    Society for Cell Biology, pp. 869–879, 2021.
  ista: Ishihara K, Decker F, Dos Santos Caldas PR, Pelletier JF, Loose M, Brugués
    J, Mitchison TJ. 2021. Spatial variation of microtubule depolymerization in large
    asters. Molecular Biology of the Cell. 32(9), 869–879.
  mla: Ishihara, Keisuke, et al. “Spatial Variation of Microtubule Depolymerization
    in Large Asters.” <i>Molecular Biology of the Cell</i>, vol. 32, no. 9, American
    Society for Cell Biology, 2021, pp. 869–79, doi:<a href="https://doi.org/10.1091/MBC.E20-11-0723">10.1091/MBC.E20-11-0723</a>.
  short: K. Ishihara, F. Decker, P.R. Dos Santos Caldas, J.F. Pelletier, M. Loose,
    J. Brugués, T.J. Mitchison, Molecular Biology of the Cell 32 (2021) 869–879.
date_created: 2021-05-23T22:01:45Z
date_published: 2021-04-19T00:00:00Z
date_updated: 2023-08-08T13:36:02Z
day: '19'
department:
- _id: MaLo
doi: 10.1091/MBC.E20-11-0723
ec_funded: 1
external_id:
  isi:
  - '000641574700005'
intvolume: '        32'
isi: 1
issue: '9'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/3.0/
main_file_link:
- open_access: '1'
  url: https://www.molbiolcell.org/doi/10.1091/mbc.E20-11-0723
month: '04'
oa: 1
oa_version: Published Version
page: 869-879
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: 260D98C8-B435-11E9-9278-68D0E5697425
  name: Reconstitution of Bacterial Cell Division Using Purified Components
publication: Molecular Biology of the Cell
publication_identifier:
  eissn:
  - 1939-4586
  issn:
  - 1059-1524
publication_status: published
publisher: American Society for Cell Biology
quality_controlled: '1'
scopus_import: '1'
status: public
title: Spatial variation of microtubule depolymerization in large asters
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  short: CC BY-NC-SA (3.0)
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volume: 32
year: '2021'
...
---
_id: '5992'
abstract:
- lang: eng
  text: Lamellipodia are flat membrane protrusions formed during mesenchymal motion.
    Polymerization at the leading edge assembles the actin filament network and generates
    protrusion force. How this force is supported by the network and how the assembly
    rate is shared between protrusion and network retrograde flow determines the protrusion
    rate. We use mathematical modeling to understand experiments changing the F-actin
    density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex
    activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction
    of density with a decrease of protrusion velocity, an increase in the ratio of
    force to filament number, but constant network assembly rate. The relation between
    protrusion force and tension gradient in the F-actin network and the density dependency
    of friction, elasticity, and viscosity of the network explain the experimental
    observations. The formins act as filament nucleators and elongators with differential
    rates. Modulation of their activity suggests an effect on network assembly rate.
    Contrary to these expectations, the effect of changes in elongator composition
    is much weaker than the consequences of the density change. We conclude that the
    force acting on the leading edge membrane is the force required to drive F-actin
    network retrograde flow.
article_processing_charge: No
author:
- first_name: Setareh
  full_name: Dolati, Setareh
  last_name: Dolati
- first_name: Frieda
  full_name: Kage, Frieda
  last_name: Kage
- first_name: Jan
  full_name: Mueller, Jan
  last_name: Mueller
- first_name: Mathias
  full_name: Müsken, Mathias
  last_name: Müsken
- first_name: Marieluise
  full_name: Kirchner, Marieluise
  last_name: Kirchner
- first_name: Gunnar
  full_name: Dittmar, Gunnar
  last_name: Dittmar
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Klemens
  full_name: Rottner, Klemens
  last_name: Rottner
- first_name: Martin
  full_name: Falcke, Martin
  last_name: Falcke
citation:
  ama: Dolati S, Kage F, Mueller J, et al. On the relation between filament density,
    force generation, and protrusion rate in mesenchymal cell motility. <i>Molecular
    Biology of the Cell</i>. 2018;29(22):2674-2686. doi:<a href="https://doi.org/10.1091/mbc.e18-02-0082">10.1091/mbc.e18-02-0082</a>
  apa: Dolati, S., Kage, F., Mueller, J., Müsken, M., Kirchner, M., Dittmar, G., …
    Falcke, M. (2018). On the relation between filament density, force generation,
    and protrusion rate in mesenchymal cell motility. <i>Molecular Biology of the
    Cell</i>. American Society for Cell Biology . <a href="https://doi.org/10.1091/mbc.e18-02-0082">https://doi.org/10.1091/mbc.e18-02-0082</a>
  chicago: Dolati, Setareh, Frieda Kage, Jan Mueller, Mathias Müsken, Marieluise Kirchner,
    Gunnar Dittmar, Michael K Sixt, Klemens Rottner, and Martin Falcke. “On the Relation
    between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal
    Cell Motility.” <i>Molecular Biology of the Cell</i>. American Society for Cell
    Biology , 2018. <a href="https://doi.org/10.1091/mbc.e18-02-0082">https://doi.org/10.1091/mbc.e18-02-0082</a>.
  ieee: S. Dolati <i>et al.</i>, “On the relation between filament density, force
    generation, and protrusion rate in mesenchymal cell motility,” <i>Molecular Biology
    of the Cell</i>, vol. 29, no. 22. American Society for Cell Biology , pp. 2674–2686,
    2018.
  ista: Dolati S, Kage F, Mueller J, Müsken M, Kirchner M, Dittmar G, Sixt MK, Rottner
    K, Falcke M. 2018. On the relation between filament density, force generation,
    and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell.
    29(22), 2674–2686.
  mla: Dolati, Setareh, et al. “On the Relation between Filament Density, Force Generation,
    and Protrusion Rate in Mesenchymal Cell Motility.” <i>Molecular Biology of the
    Cell</i>, vol. 29, no. 22, American Society for Cell Biology , 2018, pp. 2674–86,
    doi:<a href="https://doi.org/10.1091/mbc.e18-02-0082">10.1091/mbc.e18-02-0082</a>.
  short: S. Dolati, F. Kage, J. Mueller, M. Müsken, M. Kirchner, G. Dittmar, M.K.
    Sixt, K. Rottner, M. Falcke, Molecular Biology of the Cell 29 (2018) 2674–2686.
date_created: 2019-02-14T12:25:47Z
date_published: 2018-11-01T00:00:00Z
date_updated: 2023-09-19T14:30:23Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1091/mbc.e18-02-0082
external_id:
  isi:
  - '000455641000011'
  pmid:
  - '30156465'
file:
- access_level: open_access
  checksum: e98465b4416b3e804c47f40086932af2
  content_type: application/pdf
  creator: kschuh
  date_created: 2019-02-14T12:34:29Z
  date_updated: 2020-07-14T12:47:15Z
  file_id: '5994'
  file_name: 2018_ASCB_Dolati.pdf
  file_size: 6668971
  relation: main_file
file_date_updated: 2020-07-14T12:47:15Z
has_accepted_license: '1'
intvolume: '        29'
isi: 1
issue: '22'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '11'
oa: 1
oa_version: Published Version
page: 2674-2686
pmid: 1
publication: Molecular Biology of the Cell
publication_identifier:
  eissn:
  - 1939-4586
publication_status: published
publisher: 'American Society for Cell Biology '
quality_controlled: '1'
scopus_import: '1'
status: public
title: On the relation between filament density, force generation, and protrusion
  rate in mesenchymal cell motility
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 29
year: '2018'
...