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 Bioljournal_title
Nature cell biologyauthors
Nishiya N,Kiosses WB,Han J,Ginsberg MHdoi
10.1038/ncb1234keywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
343-52issue
4eissn
1465-7392issn
1476-4679pii
ncb1234journal_volume
7pub_type
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