Arp2/3 complex is critical for lamellipodia and organization of cell-matrix adhesion but dispensable for fibroblast chemotaxis

• Published in: Cell 2012-03, Vol.148 (5), p.973-987
• Main Authors: Wu, Congying, Asokan, Sreeja B., Berginski, Matthew E., Haynes, Elizabeth M., Sharpless, Norman E., Griffith, Jack D., Gomez, Shawn M., Bear, James E.
• Format: Article
• Language: English
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2011.12.034

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.