Spermidine/spermine N super(1)-acetyltransferase specifically binds to the integrin alpha 9 subunit cytoplasmic domain and enhances cell migration

• Published in: The Journal of cell biology 2004-10, Vol.167 (1), p.161-170
• Main Authors: Chen, Chun, Young, Bradford A, Coleman, Catherine S, Pegg, Anthony E, Sheppard, Dean
• Format: Article
• Language: English
• ISSN: 0021-9525

The integrin alpha 9beta1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. alpha 9beta1, like the structurally related integrin alpha 4beta1, mediates accelerated cell migration, an effect that depends on the alpha 9 cytoplasmic domain. alpha 4beta1 enhances migration through reversible binding to the adapter protein, paxillin, but alpha 9beta1-dependent migration is paxillin independent. Using yeast two-hybrid screening, we identified the polyamine catabolizing enzyme spermidine/spermine N super(1)-acetyltransferase (SSAT) as a specific binding partner of the alpha 9 cytoplasmic domain. Overexpression of SSAT increased alpha 9beta1-mediated migration, and small interfering RNA knockdown of SSAT inhibited this migration without affecting cell adhesion or migration that was mediated by other integrin cytoplasmic domains. The enzyme activity of SSAT is critical for this effect, because a catalytically inactive version did not enhance migration. We conclude that SSAT directly binds to the alpha 9 cytoplasmic domain and mediates alpha 9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates.