Article abstract
Nature Cell Biology 7, 343 - 352 (2005)
Published online: 27 March 2005 | doi:10.1038/ncb1234
There is an Erratum (May 2005) associated with this Article.
An 
4 integrin–paxillin–Arf-GAP complex restricts Rac activation to the leading edge of migrating cells
Naoyuki Nishiya1, William B. Kiosses2, Jaewon Han1 & Mark H. Ginsberg1
Abstract
Formation of a stable lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of 
4 integrin phosphorylation to the leading edge limits the interaction of 4 with paxillin to the sides and rear of a migrating cell. The 4–paxillin complex inhibits stable lamellipodia, thus confining lamellipod formation to the cell anterior. Here we report that binding of paxillin to the 4 integrin subunit inhibits adhesion-dependent lamellipodium formation by blocking Rac activation. The paxillin LD4 domain mediates this reduction in Rac activity by recruiting an ADP-ribosylation factor GTPase-activating protein (Arf-GAP) that decreases Arf activity, thereby inhibiting Rac. Finally, the localized formation of the 4–paxillin–Arf-GAP complex mediates the polarization of Rac activity and promotes directional cell migration. These findings establish a mechanism for the spatial localization of Rac activity to enhance cell migration.
- Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0726, USA.
- The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Correspondence to: Mark H. Ginsberg1 e-mail: mhginsberg@ucsd.edu
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