Cited by 125Cellular Mechanics and InteractionsMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling
Microtubules control cellular shape and coherence in amoeboid migrating cells
Open accessKopf, Aglaja, Renkawitz, Jörg, Hauschild, Robert, Girkontaite, Irute, Tedford, Kerry, Merrin, Jack, Thorn-Seshold, Oliver, Trauner, Dirk +4 more·2020·Journal of Cell Biology
DOI 10.1083/jcb.201907154PMC PMC7265309
Published version of a preprint
Abstract
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.
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GEF-H1 can control RhoA activity in response to local changes in the density of dynamic microtubules near the cell margin, e.g., to promote cell invasion or trigger cell retraction and help migrating dendritic cells maintain coherence.
“In this way, GEF-H1 can control RhoA activity in response to local changes in the density of dynamic microtubules near the cell margin, for example, to promote cell invasion into a dense matrix or trigger cell retraction and help cells with long and elaborate protrusions, such as migrating dendritic cells, to maintain their coherence 21,24-26 .”
From Taxane-induced conformational changes in the microtubule lattice activate GEF-H1-dependent RhoA signalling (2026) · cites this paper as [26]
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- Authors
- Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., Thorn-Seshold, O., Trauner, D., Häcker, H., Fischer, K.-D., Kiermaier, E., & Sixt, M.
- Affiliations
- Institute of Science and Technology Austria (AT)
- State Research Institute Centre for Innovative Medicine (LT)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Department of Pharmacy, Ludwig-Maximilians University of Munich, Munich, Germany 5
- New York University (US)
- University of Utah (US)
- University of Bonn (DE)
- Corresponding author
- Sixt, Michael
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2020-05-07
- Volume
- 219
- Issue
- 6
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC7265309
- OpenAlex
- W3023247597
- Cited by
- 125
- References
- 42
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 25 · 2023: 16 · 2022: 16 · 2021: 18 · 2020: 12
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- European Research Council (ERC StG 281556, CoG 724373)
- German Research Foundation (DFG SFB1032)
- Seventh Framework Programme (FP7/2007-2013, 291734)
- European Commission (LTFCOFUND2013, GA-2013-609409)
- DFG (EXC 2151—390873048)
- American Lebanese Syrian Associated Charities
- Ministry of Economics, Science, and Digitisation
- Austrian Science Fund (P29911, W1250-B20)
- European Molecular Biology Organization (ALTF 1396-2014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- microtubules, amoeboid cell migration, dendritic cells, actomyosin contractility, RhoA, myosin localization, cell shape regulation, cell fragmentation, proprioception, microtubule dynamics
- MeSH terms
- Actomyosin, Animals, Cell Adhesion, Cell Movement, Cells, Cultured, Dendritic Cells, Female, Mice, Inbred C57BL, Microtubules, Protein Binding, Nocodazole, Mice, Knockout, rhoA GTP-Binding Protein, Microtubule-Organizing Center, Cell Shape, Mice, Rho Guanine Nucleotide Exchange Factors
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