Degrading Polyamines for Migration

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Science  06 Jun 2008:
Vol. 320, Issue 5881, pp. 1263
DOI: 10.1126/science.320.5881.1263c

Integrins are heterodimeric transmembrane proteins that mediate cell adhesion and migration. The α9 subunit binds the spermidine/spermine-N1-acetyl-transferase SSAT, which induces the breakdown of the higher-order polyamines spermidine and spermine to the lower-order polyamine putrescine, and this interaction is required for migration mediated by the α9β1 integrin. DeHart et al. show that α9 recruitment of SSAT to focal adhesions affects cell migration by modulating the activity of an inward rectifier K+ (Kir) channel. The expression of catalytically inactive SSAT inhibited migration, suggesting that polyamine metabolism is important for α9-dependent migration. Higher-order polyamines inhibit Kir channels, and inhibition or knockdown of the Kir4.2 channel inhibited migration of the cells on α9-specific substrates but did not impair migration on fibronectin. Although α9 was present in focal adhesion-ike structures throughout the cell surface, Kir4.2 only colocalized with α9 in focal adhesion-like structures at the leading edge of the cell. Thus, the authors propose that local changes in polyamine concentrations are mediated by SSAT that is recruited to the α9 subunit of integrins; the inhibition of Kir channels allows a localized K+ efflux, which stimulates migration. — AMV

Proc. Natl. Acad. Sci. U.S.A. 105, 7188 (2008).

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