Spermidine/spermine N1-acetyltransferase specifically binds to the integrin α9 subunit cytoplasmic domain and enhances cell migration

Chun Chen, Bradford A. Young, Catherine S. Coleman, Anthony E. Pegg, Dean Sheppard

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The integrin α9β1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. α9β1, like the structurally related integrin α4β1, mediates accelerated cell migration, an effect that depends on the α9 cytoplasmic domain. α4β1 enhances migration through reversible binding to the adapter protein, paxillin, but α9β1- dependent migration is paxillin independent. Using yeast two-hybrid screening, we identified the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase (SSAT) as a specific binding partner of the α9 cytoplasmic domain. Overexpression of SSAT increased α9β1-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 α9 cytoplasmic domain and mediates α9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalJournal of Cell Biology
Volume167
Issue number1
DOIs
StatePublished - Oct 11 2004

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Spermine
Integrins
Cell Movement
Paxillin
Polyamines
Enzymes
Acetylation
Cell Adhesion
Small Interfering RNA
Leukocytes
Yeasts
diamine N-acetyltransferase
Ligands
Inflammation
Wounds and Injuries
Proteins

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Chen, Chun ; Young, Bradford A. ; Coleman, Catherine S. ; Pegg, Anthony E. ; Sheppard, Dean. / Spermidine/spermine N1-acetyltransferase specifically binds to the integrin α9 subunit cytoplasmic domain and enhances cell migration. In: Journal of Cell Biology. 2004 ; Vol. 167, No. 1. pp. 161-170.
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Spermidine/spermine N1-acetyltransferase specifically binds to the integrin α9 subunit cytoplasmic domain and enhances cell migration. / Chen, Chun; Young, Bradford A.; Coleman, Catherine S.; Pegg, Anthony E.; Sheppard, Dean.

In: Journal of Cell Biology, Vol. 167, No. 1, 11.10.2004, p. 161-170.

Research output: Contribution to journalArticle

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