The α9β1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel

The alpha 9 beta 1 integrin accelerates cell migration through binding of spermidine/spermine acetyltransferase (SSAT) to the alpha 9 cytoplasmic domain. We now show that SSAT enhances alpha 9-mediated migration specifically through catabolism of spermidine and/or spermine. Because spermine and spermidine are effective blockers of K(+) ion efflux through inward-rectifier K(+) (Kir) channels, we examined the involvement of Kir channels in this pathway. The Kir channel inhibitor, barium, or knockdown of a single subunit, Kir4.2, specifically inhibited alpha 9-dependent cell migration. alpha 9 beta 1 and Kir4.2 colocalized in focal adhesions at the leading edge of migrating cells and inhibition or knockdown of Kir4.2 caused reduced persistence and an increased number of lamellipodial extensions in cells migrating on an alpha 9 beta 1 ligand. These results identify a pathway through which the alpha 9 integrin subunit stimulates cell migration by localized polyamine catabolism and modulation of Kir channel function.