The cytoplasmic domain of the integrin alpha 9 subunit requires the adaptor protein paxillin to inhibit cell spreading but promotes cell migration ina paxillin-independent manner

The integrin alpha9 subunit forms a single heterodimer, alpha9 beta1. The a lpha9 subunit is most closely related to the alpha4 subunit, and like alpha 4 integrins, alpha9 beta1 plays an important role in leukocyte migration. T he A cytoplasmic domain preferentially enhances cell migration and inhibits cell spreading, effects that depend on interaction with the adaptor protei n, paxillin. To determine whether the alpha9 cytoplasmic domain has similar effects, a series of chimeric and deleted alpha9 constructs were expressed in Chinese hamster ovary cells and tested for their effects on migration a nd spreading on an alpha9 beta1-specific ligand. Like alpha4, the alpha9 cy toplasmic domain enhanced cell migration and inhibited cell spreading. Paxi llin also specifically bound the alpha9 cytoplasmic domain and to a similar level as alpha4. In paxillin(-/-) cells, alpha9 failed to inhibit cell spr eading as expected but surprisingly still enhanced cell migration. Further, mutations that abolished the alpha9-paxillin interaction prevented alpha9 from inhibiting cell spreading but had no effect on alpha9-dependent cell m igration. These findings suggest that the mechanisms by which the cytoplasm ic domains of integrin a subunits enhance migration and inhibit cell spread ing are distinct and that the alpha9 and alpha4 cytoplasmic domains, despit e sequence and functional similarities, enhance cell migration by different intracellular signaling pathways.