The α9β1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel
- *Lung Biology Center, Department of Medicine, and
- †Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, CA 94143; and
- ‡Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033
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Edited by Lily Y. Jan, University of California School of Medicine, San Francisco, CA, and approved March 11, 2008 (received for review August 27, 2007)
Abstract
The α9β1 integrin accelerates cell migration through binding of spermidine/spermine acetyltransferase (SSAT) to the α9 cytoplasmic domain. We now show that SSAT enhances α9-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 α9-dependent cell migration. α9β1 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 α9β1 ligand. These results identify a pathway through which the α9 integrin subunit stimulates cell migration by localized polyamine catabolism and modulation of Kir channel function.
Footnotes
- §To whom correspondence should be addressed at: Box 2922, University of California, San Francisco, CA 94143-2922. E-mail: dean.sheppard{at}ucsf.edu
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Author contributions: G.W.d. and D.S. designed research; G.W.d. and T.J. performed research; T.J., D.E.M., and A.E.P. contributed new reagents/analytic tools; G.W.d., T.J., D.E.M., and A.E.P. analyzed data; and G.W.d. and D.S. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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See Commentary on page 7109.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0708044105/DCSupplemental.
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Freely available online through the PNAS open access option.
- © 2008 by The National Academy of Sciences of the USA
