An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells.

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.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Nishiya N,Kiosses WB,Han J,Ginsberg MH

doi

10.1038/ncb1234

keywords:

subject

Has Abstract

pub_date

2005-04-01 00:00:00

pages

343-52

issue

4

eissn

1465-7392

issn

1476-4679

pii

ncb1234

journal_volume

7

pub_type

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