An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells - PubMed (original) (raw)
doi: 10.1038/ncb1234. Epub 2005 Mar 27.
Affiliations
- PMID: 15793570
- DOI: 10.1038/ncb1234
An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells
Naoyuki Nishiya et al. Nat Cell Biol. 2005 Apr.
Erratum in
- Nat Cell Biol. 2005 May;7(5):531
Abstract
Formation of a stable lamellipodium at the front of migrating cells requires localization of Rac activation to the leading edge. Restriction of alpha4 integrin phosphorylation to the leading edge limits the interaction of alpha4 with paxillin to the sides and rear of a migrating cell. The alpha4-paxillin complex inhibits stable lamellipodia, thus confining lamellipod formation to the cell anterior. Here we report that binding of paxillin to the alpha4 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 alpha4-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.
Comment in
- Cell polarization mechanisms during directed cell migration.
Huttenlocher A. Huttenlocher A. Nat Cell Biol. 2005 Apr;7(4):336-7. doi: 10.1038/ncb0405-336. Nat Cell Biol. 2005. PMID: 15803131 No abstract available.
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