---
_id: '7875'
abstract:
- lang: eng
  text: 'Cells navigating through complex tissues face a fundamental challenge: while
    multiple protrusions explore different paths, the cell needs to avoid entanglement.
    How a cell surveys and then corrects its own shape is poorly understood. Here,
    we demonstrate that spatially distinct microtubule dynamics regulate amoeboid
    cell migration by locally promoting the retraction of protrusions. In migrating
    dendritic cells, local microtubule depolymerization within protrusions remote
    from the microtubule organizing center triggers actomyosin contractility controlled
    by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin
    localization, thereby causing two effects that rate-limit locomotion: (1) impaired
    cell edge coordination during path finding and (2) defective adhesion resolution.
    Compromised shape control is particularly hindering in geometrically complex microenvironments,
    where it leads to entanglement and ultimately fragmentation of the cell body.
    We thus demonstrate that microtubules can act as a proprioceptive device: they
    sense cell shape and control actomyosin retraction to sustain cellular coherence.'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (Life Sciences, Bioimaging,
  Preclinical) of the Institute of Science and Technology Austria for excellent support.
  This work was funded by the European Research Council (ERC StG 281556 and CoG 724373),
  two grants from the Austrian\r\nScience Fund (FWF; P29911 and DK Nanocell W1250-B20
  to M. Sixt) and by the German Research Foundation (DFG SFB1032 project B09) to O.
  Thorn-Seshold and D. Trauner. J. Renkawitz was supported by ISTFELLOW funding from
  the People Program (Marie Curie Actions) of the European Union’s Seventh Framework
  Programme (FP7/2007-2013) under the Research Executive Agency grant agreement (291734)
  and a European Molecular Biology Organization long-term fellowship (ALTF 1396-2014)
  co-funded by the European Commission (LTFCOFUND2013, GA-2013-609409), E. Kiermaier
  by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s
  Excellence Strategy—EXC 2151—390873048, and H. Hacker by the American Lebanese Syrian
  Associated ¨Charities. K.-D. Fischer was supported by the Analysis, Imaging and
  Modelling of Neuronal and Inflammatory Processes graduate school funded by the Ministry
  of Economics, Science, and Digitisation of the State Saxony-Anhalt and by the European
  Funds for Social and Regional Development."
article_number: e201907154
article_processing_charge: No
article_type: original
author:
- first_name: Aglaja
  full_name: Kopf, Aglaja
  id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
  last_name: Kopf
  orcid: 0000-0002-2187-6656
- first_name: Jörg
  full_name: Renkawitz, Jörg
  id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
  last_name: Renkawitz
  orcid: 0000-0003-2856-3369
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Irute
  full_name: Girkontaite, Irute
  last_name: Girkontaite
- first_name: Kerry
  full_name: Tedford, Kerry
  last_name: Tedford
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Oliver
  full_name: Thorn-Seshold, Oliver
  last_name: Thorn-Seshold
- first_name: Dirk
  full_name: Trauner, Dirk
  id: E8F27F48-3EBA-11E9-92A1-B709E6697425
  last_name: Trauner
- first_name: Hans
  full_name: Häcker, Hans
  last_name: Häcker
- first_name: Klaus Dieter
  full_name: Fischer, Klaus Dieter
  last_name: Fischer
- first_name: Eva
  full_name: Kiermaier, Eva
  id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
  last_name: Kiermaier
  orcid: 0000-0001-6165-5738
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Kopf A, Renkawitz J, Hauschild R, et al. Microtubules control cellular shape
    and coherence in amoeboid migrating cells. <i>The Journal of Cell Biology</i>.
    2020;219(6). doi:<a href="https://doi.org/10.1083/jcb.201907154">10.1083/jcb.201907154</a>
  apa: Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin,
    J., … Sixt, M. K. (2020). Microtubules control cellular shape and coherence in
    amoeboid migrating cells. <i>The Journal of Cell Biology</i>. Rockefeller University
    Press. <a href="https://doi.org/10.1083/jcb.201907154">https://doi.org/10.1083/jcb.201907154</a>
  chicago: Kopf, Aglaja, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry
    Tedford, Jack Merrin, Oliver Thorn-Seshold, et al. “Microtubules Control Cellular
    Shape and Coherence in Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>.
    Rockefeller University Press, 2020. <a href="https://doi.org/10.1083/jcb.201907154">https://doi.org/10.1083/jcb.201907154</a>.
  ieee: A. Kopf <i>et al.</i>, “Microtubules control cellular shape and coherence
    in amoeboid migrating cells,” <i>The Journal of Cell Biology</i>, vol. 219, no.
    6. Rockefeller University Press, 2020.
  ista: Kopf A, Renkawitz J, Hauschild R, Girkontaite I, Tedford K, Merrin J, Thorn-Seshold
    O, Trauner D, Häcker H, Fischer KD, Kiermaier E, Sixt MK. 2020. Microtubules control
    cellular shape and coherence in amoeboid migrating cells. The Journal of Cell
    Biology. 219(6), e201907154.
  mla: Kopf, Aglaja, et al. “Microtubules Control Cellular Shape and Coherence in
    Amoeboid Migrating Cells.” <i>The Journal of Cell Biology</i>, vol. 219, no. 6,
    e201907154, Rockefeller University Press, 2020, doi:<a href="https://doi.org/10.1083/jcb.201907154">10.1083/jcb.201907154</a>.
  short: A. Kopf, J. Renkawitz, R. Hauschild, I. Girkontaite, K. Tedford, J. Merrin,
    O. Thorn-Seshold, D. Trauner, H. Häcker, K.D. Fischer, E. Kiermaier, M.K. Sixt,
    The Journal of Cell Biology 219 (2020).
date_created: 2020-05-24T22:00:56Z
date_published: 2020-06-01T00:00:00Z
date_updated: 2023-08-21T06:28:17Z
day: '01'
ddc:
- '570'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1083/jcb.201907154
ec_funded: 1
external_id:
  isi:
  - '000538141100020'
  pmid:
  - '32379884'
file:
- access_level: open_access
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  creator: dernst
  date_created: 2020-11-24T13:25:13Z
  date_updated: 2020-11-24T13:25:13Z
  file_id: '8801'
  file_name: 2020_JCellBiol_Kopf.pdf
  file_size: 7536712
  relation: main_file
  success: 1
file_date_updated: 2020-11-24T13:25:13Z
has_accepted_license: '1'
intvolume: '       219'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P29911
  name: Mechanical adaptation of lamellipodial actin
- _id: 252C3B08-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W 1250-B20
  name: Nano-Analytics of Cellular Systems
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1396-2014
  name: Molecular and system level view of immune cell migration
publication: The Journal of Cell Biology
publication_identifier:
  eissn:
  - 1540-8140
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Microtubules control cellular shape and coherence in amoeboid migrating cells
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 219
year: '2020'
...
---
_id: '6328'
abstract:
- lang: eng
  text: During metazoan development, immune surveillance and cancer dissemination,
    cells migrate in complex three-dimensional microenvironments1,2,3. These spaces
    are crowded by cells and extracellular matrix, generating mazes with differently
    sized gaps that are typically smaller than the diameter of the migrating cell4,5.
    Most mesenchymal and epithelial cells and some—but not all—cancer cells actively
    generate their migratory path using pericellular tissue proteolysis6. By contrast,
    amoeboid cells such as leukocytes use non-destructive strategies of locomotion7,
    raising the question how these extremely fast cells navigate through dense tissues.
    Here we reveal that leukocytes sample their immediate vicinity for large pore
    sizes, and are thereby able to choose the path of least resistance. This allows
    them to circumnavigate local obstacles while effectively following global directional
    cues such as chemotactic gradients. Pore-size discrimination is facilitated by
    frontward positioning of the nucleus, which enables the cells to use their bulkiest
    compartment as a mechanical gauge. Once the nucleus and the closely associated
    microtubule organizing centre pass the largest pore, cytoplasmic protrusions still
    lingering in smaller pores are retracted. These retractions are coordinated by
    dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence
    and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning
    in front of the microtubule organizing centre is a typical feature of amoeboid
    migration, our findings link the fundamental organization of cellular polarity
    to the strategy of locomotion.
acknowledged_ssus:
- _id: SSU
article_processing_charge: No
article_type: letter_note
author:
- first_name: Jörg
  full_name: Renkawitz, Jörg
  id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
  last_name: Renkawitz
  orcid: 0000-0003-2856-3369
- first_name: Aglaja
  full_name: Kopf, Aglaja
  id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
  last_name: Kopf
  orcid: 0000-0002-2187-6656
- first_name: Julian A
  full_name: Stopp, Julian A
  id: 489E3F00-F248-11E8-B48F-1D18A9856A87
  last_name: Stopp
- first_name: Ingrid
  full_name: de Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: de Vries
- first_name: Meghan K.
  full_name: Driscoll, Meghan K.
  last_name: Driscoll
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Erik S.
  full_name: Welf, Erik S.
  last_name: Welf
- first_name: Gaudenz
  full_name: Danuser, Gaudenz
  last_name: Danuser
- first_name: Reto
  full_name: Fiolka, Reto
  last_name: Fiolka
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Renkawitz J, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid
    migration along the path of least resistance. <i>Nature</i>. 2019;568:546-550.
    doi:<a href="https://doi.org/10.1038/s41586-019-1087-5">10.1038/s41586-019-1087-5</a>
  apa: Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin,
    J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along
    the path of least resistance. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-019-1087-5">https://doi.org/10.1038/s41586-019-1087-5</a>
  chicago: Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K.
    Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates
    Amoeboid Migration along the Path of Least Resistance.” <i>Nature</i>. Springer
    Nature, 2019. <a href="https://doi.org/10.1038/s41586-019-1087-5">https://doi.org/10.1038/s41586-019-1087-5</a>.
  ieee: J. Renkawitz <i>et al.</i>, “Nuclear positioning facilitates amoeboid migration
    along the path of least resistance,” <i>Nature</i>, vol. 568. Springer Nature,
    pp. 546–550, 2019.
  ista: Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild
    R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates
    amoeboid migration along the path of least resistance. Nature. 568, 546–550.
  mla: Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration
    along the Path of Least Resistance.” <i>Nature</i>, vol. 568, Springer Nature,
    2019, pp. 546–50, doi:<a href="https://doi.org/10.1038/s41586-019-1087-5">10.1038/s41586-019-1087-5</a>.
  short: J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin,
    R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550.
date_created: 2019-04-17T06:52:28Z
date_published: 2019-04-25T00:00:00Z
date_updated: 2024-03-25T23:30:22Z
day: '25'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
doi: 10.1038/s41586-019-1087-5
ec_funded: 1
external_id:
  isi:
  - '000465594200050'
  pmid:
  - '30944468'
intvolume: '       568'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/
month: '04'
oa: 1
oa_version: Submitted Version
page: 546-550
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
    (EU)
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 265FAEBA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01250-B20
  name: Nano-Analytics of Cellular Systems
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1396-2014
  name: Molecular and system level view of immune cell migration
publication: Nature
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/
  record:
  - id: '14697'
    relation: dissertation_contains
    status: public
  - id: '6891'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Nuclear positioning facilitates amoeboid migration along the path of least
  resistance
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 568
year: '2019'
...
---
_id: '15'
abstract:
- lang: eng
  text: Although much is known about the physiological framework of T cell motility,
    and numerous rate-limiting molecules have been identified through loss-of-function
    approaches, an integrated functional concept of T cell motility is lacking. Here,
    we used in vivo precision morphometry together with analysis of cytoskeletal dynamics
    in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic
    organs. We show that the contributions of the integrin LFA-1 and the chemokine
    receptor CCR7 are complementary rather than positioned in a linear pathway, as
    they are during leukocyte extravasation from the blood vasculature. Our data demonstrate
    that CCR7 controls cortical actin flows, whereas integrins mediate substrate friction
    that is sufficient to drive locomotion in the absence of considerable surface
    adhesions and plasma membrane flux.
acknowledged_ssus:
- _id: SSU
acknowledgement: This work was funded by grants from the European Research Council
  (ERC StG 281556 and CoG 724373) and the Austrian Science Foundation (FWF) to M.S.
  and by Swiss National Foundation (SNF) project grants 31003A_135649, 31003A_153457
  and CR23I3_156234 to J.V.S. F.G. received funding from the European Union’s Horizon
  2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement
  no. 747687, and J.R. was funded by an EMBO long-term fellowship (ALTF 1396-2014).
article_processing_charge: No
author:
- first_name: Miroslav
  full_name: Hons, Miroslav
  id: 4167FE56-F248-11E8-B48F-1D18A9856A87
  last_name: Hons
  orcid: 0000-0002-6625-3348
- first_name: Aglaja
  full_name: Kopf, Aglaja
  id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
  last_name: Kopf
  orcid: 0000-0002-2187-6656
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
  orcid: 0000-0002-1073-744X
- first_name: Florian R
  full_name: Gärtner, Florian R
  id: 397A88EE-F248-11E8-B48F-1D18A9856A87
  last_name: Gärtner
  orcid: 0000-0001-6120-3723
- first_name: Jun
  full_name: Abe, Jun
  last_name: Abe
- first_name: Jörg
  full_name: Renkawitz, Jörg
  id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
  last_name: Renkawitz
  orcid: 0000-0003-2856-3369
- first_name: Jens
  full_name: Stein, Jens
  last_name: Stein
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Hons M, Kopf A, Hauschild R, et al. Chemokines and integrins independently
    tune actin flow and substrate friction during intranodal migration of T cells.
    <i>Nature Immunology</i>. 2018;19(6):606-616. doi:<a href="https://doi.org/10.1038/s41590-018-0109-z">10.1038/s41590-018-0109-z</a>
  apa: Hons, M., Kopf, A., Hauschild, R., Leithner, A. F., Gärtner, F. R., Abe, J.,
    … Sixt, M. K. (2018). Chemokines and integrins independently tune actin flow and
    substrate friction during intranodal migration of T cells. <i>Nature Immunology</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/s41590-018-0109-z">https://doi.org/10.1038/s41590-018-0109-z</a>
  chicago: Hons, Miroslav, Aglaja Kopf, Robert Hauschild, Alexander F Leithner, Florian
    R Gärtner, Jun Abe, Jörg Renkawitz, Jens Stein, and Michael K Sixt. “Chemokines
    and Integrins Independently Tune Actin Flow and Substrate Friction during Intranodal
    Migration of T Cells.” <i>Nature Immunology</i>. Nature Publishing Group, 2018.
    <a href="https://doi.org/10.1038/s41590-018-0109-z">https://doi.org/10.1038/s41590-018-0109-z</a>.
  ieee: M. Hons <i>et al.</i>, “Chemokines and integrins independently tune actin
    flow and substrate friction during intranodal migration of T cells,” <i>Nature
    Immunology</i>, vol. 19, no. 6. Nature Publishing Group, pp. 606–616, 2018.
  ista: Hons M, Kopf A, Hauschild R, Leithner AF, Gärtner FR, Abe J, Renkawitz J,
    Stein J, Sixt MK. 2018. Chemokines and integrins independently tune actin flow
    and substrate friction during intranodal migration of T cells. Nature Immunology.
    19(6), 606–616.
  mla: Hons, Miroslav, et al. “Chemokines and Integrins Independently Tune Actin Flow
    and Substrate Friction during Intranodal Migration of T Cells.” <i>Nature Immunology</i>,
    vol. 19, no. 6, Nature Publishing Group, 2018, pp. 606–16, doi:<a href="https://doi.org/10.1038/s41590-018-0109-z">10.1038/s41590-018-0109-z</a>.
  short: M. Hons, A. Kopf, R. Hauschild, A.F. Leithner, F.R. Gärtner, J. Abe, J. Renkawitz,
    J. Stein, M.K. Sixt, Nature Immunology 19 (2018) 606–616.
date_created: 2018-12-11T11:44:10Z
date_published: 2018-05-18T00:00:00Z
date_updated: 2024-03-25T23:30:22Z
day: '18'
department:
- _id: MiSi
- _id: Bio
doi: 10.1038/s41590-018-0109-z
ec_funded: 1
external_id:
  isi:
  - '000433041500026'
  pmid:
  - '29777221'
intvolume: '        19'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pubmed/29777221
month: '05'
oa: 1
oa_version: Published Version
page: 606 - 616
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '747687'
  name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 1396-2014
  name: Molecular and system level view of immune cell migration
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '281556'
  name: Cytoskeletal force generation and force transduction of migrating leukocytes
    (EU)
publication: Nature Immunology
publication_status: published
publisher: Nature Publishing Group
publist_id: '8040'
quality_controlled: '1'
related_material:
  record:
  - id: '6891'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Chemokines and integrins independently tune actin flow and substrate friction
  during intranodal migration of T cells
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 19
year: '2018'
...