title: Arp2/3 is critical for lamellipodia and response to extracellular matrix cues but is dispensable for chemotaxis.
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.
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Congying
authors.initials: C
authors.lastname: Wu
authors.forename: Sreeja B
authors.initials: SB
authors.lastname: Asokan
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Berginski
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Haynes
authors.forename: Norman E
authors.initials: NE
authors.lastname: Sharpless
authors.forename: Jack D
authors.initials: JD
authors.lastname: Griffith
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Gomez
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002633:Chemotaxis; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D022001:Focal Adhesions; D051379:Mice; D011554:Pseudopodia / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex