The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Arp2/3 Is Critical for Lamellipodia and Response to Extracellular Matrix Cues but Is Dispensable for Chemotaxis
Open accessAbstract
SUMMARY Lamellipodia are sheet-like, leading edge protrusions in firmly adherent cells that contain Arp2/3-generated dendritic actin networks. Although lamellipodia are widely believed to be critical for directional cell motility, this notion has not been rigorously tested. Using fibroblasts derived from Ink4a/Arf-deficient mice, we generated a stable line depleted of Arp2/3 complex that lacks lamellipodia. This line shows defective random cell motility and relies on a filopodia-based protrusion system. Utilizing a microfluidic gradient generation system, we tested the role of Arp2/3 complex and lamellipodia in directional cell migration. Surprisingly, Arp2/3-depleted cells respond normally to shallow gradients of PDGF indicating that lamellipodia are not required for fibroblast chemotaxis. Conversely, these cells cannot respond to a surface-bound gradient of extracellular matrix (haptotaxis). Consistent with this finding, cells depleted of Arp2/3 fail to globally align focal adhesions suggesting that one principle function of lamellipodia is to organize cell-matrix adhesions in a spatially coherent manner.
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Cites
Cellular and molecular mechanisms of fibrosis
Wynn, T. (2008) · The Journal of Pathology · doi:10.1002/path.2277 · Cited by 4,495
Cellular and Molecular Mechanisms of Pain
Basbaum, A. I., Bautista, D. M., Scherrer, G., & Julius, D. (2009) · Cell · doi:10.1016/j.cell.2009.09.028 · Cited by 4,344
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566
The Regulation of INK4/ARF in Cancer and Aging
Kim, W. Y., & Sharpless, N. E. (2006) · Cell · doi:10.1016/j.cell.2006.10.003 · Cited by 1,009
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Cited by
Actin Dynamics, Architecture, and Mechanics in Cell Motility
Blanchoin, L., Boujemaa-Paterski, R., Sykes, C., & Plastino, J. (2014) · Physiological Reviews · doi:10.1152/physrev.00018.2013 · Cited by 1,457
Plotnikov, S. V., Pasapera, A. M., Sabass, B., & Waterman, C. M. (2012) · Cell · doi:10.1016/j.cell.2012.11.034 · Cited by 866
Mechanoreciprocity in cell migration
van Helvert, S., Storm, C., & Friedl, P. (2018) · Nature Cell Biology · doi:10.1038/s41556-017-0012-0 · Cited by 587
Case, L. B., & Waterman, C. M. (2015) · Nature Cell Biology · doi:10.1038/ncb3191 · Cited by 520
New insights into the regulation and cellular functions of the ARP2/3 complex
Rotty, J. D., Wu, C., & Bear, J. E. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3492 · Cited by 516
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Metadata
- Authors
- Wu, C., Asokan, S. B., Berginski, M. E., Haynes, E. M., Sharpless, N. E., Griffith, J. D., Gomez, S. M., & Bear, J. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 148
- Issue
- 5
- Pages
- 973-987
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1997230083
- Cited by
- 487
- References
- 4
- FWCI
- 18.53
- Type
- journal article
- Language
- en
- Open access
- bronze
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