期刊
CELL
卷 148, 期 5, 页码 973-987出版社
CELL PRESS
DOI: 10.1016/j.cell.2011.12.034
关键词
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资金
- HHMI, NIH [GM083035, UO1-CA141576, DK037871, GM31819, ES 13773]
- LCCC Electron Microscopy Core [NIH CA16086]
- UNC-Olympus Imaging Research Center, UNC Research Computing
- Allbrittion lab
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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