The Rho GTPases in Macrophage Motility and Chemotaxis
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The GTP-binding proteins, Rho, Rac and Cdc42 are known to regulate actin organisation. Rho induces the assembly of contractile actin-based microfilaments such as stress fibres, Rac regulates the formation of membrane ruffles and lamellipodia, and Cdc42 activation is necessary for the formation of filopodia. In addition, all three proteins can also regulate the assembly of integrin-containing focal adhesion complexes. The orchestration of these distinct cytoskeletal changes is thought to form the basis of the coordination of cell motility and we have investigated the roles of Rho family proteins in migration using a model system. We have found that in the macrophage cell line Bac1, the cytokine CSF-1 rapidly induces actin reorganisation: it stimulates the formation of filopodia, lamellipodia and membrane ruffles, as well as the appearance of fine actin cables within the cell. We have shown that Cdc42, Rac and Rho regulate the CSF-1 induced formation of these distinct actin filament-based structures. Using a cell tracking procedure we found that both Rho and Rac were required for CSF-1 stimulated cell translocation. In contrast, inhibition of Cdc42 does not prevent macrophages migrating in response to CSF-1, but does prevent recognition of a CSF-1 concentration gradient, so that cells now migrate randomly rather than up the gradient of this chemotactic cytokine. This implies that Cdc42, and thus probably filopodia, are required for gradient sensing and cell polarisation in macrophages.
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Macrophages, as part of their myeloid lineage, do not possess stress fibers, possibly because their interaction with surrounding matrix when not migrating is not a key part of their innate function.
“It has been shown that macrophages, as part of their myeloid lineage, do not possess stress fibers,58 which may in large part be due to the fact that their interaction with their surrounding matrix, when not migrating, is not a key part of their innate function.29”
From Student award winner in the undergraduate category for the society of biomaterials 9th World Biomaterials Congress, Chengdu, China, June 1–5, 2012: The effects of substrate stiffness on the <i>in vitro</i> activation of macrophages and <i>in vivo</i> host response to poly(ethylene glycol)‐based hydrogels (2012) · cites this paper as [58]
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- Authors
- Jones, G. E., Allen, W. E., & Ridley, A. J.
- Affiliations
- King's College London (GB)
- Corresponding author
- Jones, Gareth E.
- Venue
- Cell Adhesion and Communication
- Publisher
- Informa UK Limited
- Published
- 1998-01
- Volume
- 6
- Issue
- 2-3
- Pages
- 237-245
- ISSN
- 1023-7046 (ISSN-L)
- 1029-2314
- OpenAlex
- W2003437189
- Cited by
- 89
- References
- 40
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 7 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 0.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Communication & Adhesion (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- Rho GTPases, macrophage motility, chemotaxis, Cdc42, Rac, Rho, actin cytoskeleton, filopodia, lamellipodia, ruffles, stress fibers, CSF-1, gradient sensing, cell polarization, focal adhesions, cell tracking
- MeSH terms
- Animals, Cell Movement, Chemotaxis, Macrophages, Proteins, GTP Phosphohydrolases, GTPase-Activating Proteins
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