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Syndecan-4–dependent Rac1 regulation determines directional migration in response to the extracellular matrix
Open accessAbstract
Cell migration in wound healing and disease is critically dependent on integration with the extracellular matrix, but the receptors that couple matrix topography to migratory behavior remain obscure. Using nano-engineered fibronectin surfaces and cell-derived matrices, we identify syndecan-4 as a key signaling receptor determining directional migration. In wild-type fibroblasts, syndecan-4 mediates the matrix-induced protein kinase Cα (PKCα)–dependent activation of Rac1 and localizes Rac1 activity and membrane protrusion to the leading edge of the cell, resulting in persistent migration. In contrast, syndecan-4–null fibroblasts migrate randomly as a result of high delocalized Rac1 activity, whereas cells expressing a syndecan-4 cytodomain mutant deficient in PKCα regulation fail to localize active Rac1 to points of matrix engagement and consequently fail to recognize and respond to topographical changes in the matrix.
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Citations
Cited by
Sarrazin, S., Lamanna, W. C., & Esko, J. D. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a004952 · Cited by 1,516
Horton, E. R., Byron, A., Askari, J. A., Ng, D. H. J., Millon-Frémillon, A., Robertson, J., Koper, E. J., Paul, N. R., Warwood, S., Knight, D., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3257 · Cited by 543
Self-citationThe Extracellular Matrix Modulates the Metastatic Journey
Kai, F., Drain, A. P., & Weaver, V. M. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.03.026 · Cited by 537
Heparan sulfate proteoglycan as a cell-surface endocytosis receptor
Christianson, H. C., & Belting, M. (2014) · Matrix Biology · doi:10.1016/j.matbio.2013.10.004 · Cited by 429
Humphries, J. D., Byron, A., Bass, M. D., Craig, S. E., Pinney, J. W., Knight, D., & Humphries, M. J. (2009) · Science Signaling · doi:10.1126/scisignal.2000396 · Cited by 404
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Metadata
- Authors
- Bass, M. D., Roach, K. A., Morgan, M. R., Mostafavi-Pour, Z., Schoen, T., Muramatsu, T., Mayer, U., Ballestrem, C., Spatz, J. P., & Humphries, M. J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-05-07
- Volume
- 177
- Issue
- 3
- Pages
- 527-538
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W1974377564
- Cited by
- 236
- References
- 0
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- green
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- Bass, M. D., Roach, K. A., Morgan, M. R., Mostafavi-Pour, Z., Schoen, T., Muramatsu, T., Mayer, U., Ballestrem, C., Spatz, J. P., & Humphries, M. J. (2007). Syndecan-4–dependent Rac1 regulation determines directional migration in response to the extracellular matrix. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200610076
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