Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis.
Cell
; 148(5): 973-87, 2012 Mar 02.
Article
en En
| MEDLINE
| ID: mdl-22385962
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Seudópodos
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Movimiento Celular
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Quimiotaxis
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Complejo 2-3 Proteico Relacionado con la Actina
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Matriz Extracelular
Límite:
Animals
Idioma:
En
Año:
2012
Tipo del documento:
Article