Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 105 (20): 7188-7193

Copyright © 2008 by the National Academy of Sciences.


The {alpha}9β1 integrin enhances cell migration by polyamine-mediated modulation of an inward-rectifier potassium channel

Gregory W. deHart*, Taihao Jin{dagger}, Diane E. McCloskey{ddagger}, Anthony E. Pegg{ddagger}, and Dean Sheppard*,§

*Lung Biology Center, Department of Medicine, and {dagger}Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, CA 94143; and {ddagger}Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033

Edited by Lily Y. Jan, University of California School of Medicine, San Francisco, CA, and approved March 11, 2008

Received for publication August 27, 2007.

Abstract: The {alpha}9β1 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}9β1 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}9β1 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.

Freely available online through the PNAS open access option.

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.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

See Commentary on page 7109.

This article contains supporting information online at

§To whom correspondence should be addressed at: Box 2922, University of California, San Francisco, CA 94143-2922. E-mail: dean.sheppard{at}

© 2008 by The National Academy of Sciences of the USA

Interaction of tumour cells with their microenvironment: ion channels and cell adhesion molecules. A focus on pancreatic cancer.
A. Arcangeli, O. Crociani, and L. Bencini (2014)
Phil Trans R Soc B 369, 20130101
   Abstract »    Full Text »    PDF »
Evidence of K+ channel function in epithelial cell migration, proliferation, and repair.
A. Girault and E. Brochiero (2014)
Am J Physiol Cell Physiol 306, C307-C319
   Abstract »    Full Text »    PDF »
Role of Ion Channels and Transporters in Cell Migration.
A. Schwab, A. Fabian, P. J. Hanley, and C. Stock (2012)
Physiol Rev 92, 1865-1913
   Abstract »    Full Text »    PDF »
Polydom/SVEP1 Is a Ligand for Integrin {alpha}9{beta}1.
R. Sato-Nishiuchi, I. Nakano, A. Ozawa, Y. Sato, M. Takeichi, D. Kiyozumi, K. Yamazaki, T. Yasunaga, S. Futaki, and K. Sekiguchi (2012)
J. Biol. Chem. 287, 25615-25630
   Abstract »    Full Text »    PDF »
Ion channels and transporters in cancer. 3. Ion channels in the tumor cell-microenvironment cross talk.
A. Arcangeli (2011)
Am J Physiol Cell Physiol 301, C762-C771
   Abstract »    Full Text »    PDF »
Suppression of Exogenous Gene Expression by Spermidine/Spermine N1-Acetyltransferase 1 (SSAT1) Cotransfection.
S. B. Lee, J. H. Park, P. M. Woster, R. A. Casero Jr., and M. H. Park (2010)
J. Biol. Chem. 285, 15548-15556
   Abstract »    Full Text »    PDF »
Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles.
H. Hibino, A. Inanobe, K. Furutani, S. Murakami, I. Findlay, and Y. Kurachi (2010)
Physiol Rev 90, 291-366
   Abstract »    Full Text »    PDF »
Integrin {alpha}9{beta}1 mediates enhanced cell migration through nitric oxide synthase activity regulated by Src tyrosine kinase.
S. K. Gupta and N. E. Vlahakis (2009)
J. Cell Sci. 122, 2043-2054
   Abstract »    Full Text »    PDF »
Integrins step up the pace of cell migration through polyamines and potassium channels.
C. A. Vandenberg (2008)
PNAS 105, 7109-7110
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882