Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts
Abstract
Microtubules are involved in actin-based protrusion at the leading-edge lamellipodia of migrating fibroblasts. Here we show that the growth of microtubules induced in fibroblasts by removal of the microtubule destabilizer nocodazole activates Rac1 GTPase, leading to the polymerization of actin in lamellipodial protrusions. Lamellipodial protrusions are also activated by the rapid growth of a disorganized array of very short microtubules induced by the microtubule-stabilizing drug taxol. Thus, neither microtubule shortening nor long-range microtubule-based intracellular transport is required for activating protrusion. We suggest that the growth phase of microtubule dynamic instability at leading-edge lamellipodia locally activates Rac1 to drive actin polymerization and lamellipodial protrusion required for cell migration.
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RhoA and Rac1 pull-down assays revealed low basal levels of activity and no correlation with kinesin-13 overexpression.
“We ruled out a direct role for kinesin-13-mediated microtubule depolymerization in activating small GTPases14 by performing RhoA and Rac1 pull-down assays, which revealed low basal levels of activity and no correlation with kinesin-13 overexpression”
From Chromosomal instability drives metastasis through a cytosolic DNA response (2018) · cites this paper as [14]
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References 37 · Cited by 491
- Authors
- Waterman-Storer, C. M., Worthylake, R. A., Liu, B. P., Burridge, K., & Salmon, E. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- ORCID
- Burridge, Keith
- Venue
- Nature Cell Biology
- Published
- 1999-05
- Volume
- 1
- Issue
- 1
- Pages
- 45-50
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- DOI
- 10.1038/9018
- OpenAlex
- W1561407320
- Cited by
- 491
- References
- 37
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 9 · 2020: 16 · 2019: 13 · 2018: 17 · 2017: 11 · 2016: 13 · 2015: 21 · 2014: 28 · 2013: 14 · 2012: 22
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- 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
- microtubule growth, Rac1 GTPase, lamellipodia, cell migration, fibroblasts, actin polymerization, microtubule dynamic instability, nocodazole, paclitaxel, microtubule stabilization, leading edge protrusion
- MeSH terms
- Actins, Animals, Cell Movement, Kinetics, Microtubules, Nocodazole, 3T3 Cells, Paclitaxel, rac1 GTP-Binding Protein, Mice
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