Spermidine/spermine N1-acetyltransferase specifically binds to the integrin alpha9 subunit cytoplasmic domain and enhances cell migration.
The integrin alpha9beta1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. alpha9beta1, like the structurally related integrin alpha4beta1, mediates accelerated cell migration, an effect that depends on the alpha9 cytoplasmic domain. alpha4beta1 enhances migration through reversible binding to the adapter protein, paxillin, but alpha9beta1-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 alpha9 cytoplasmic domain. Overexpression of SSAT increased alpha9beta1-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 alpha9 cytoplasmic domain and mediates alpha9-dependent enhancement of cell migration, presumably by localized effects on acetylation of polyamines or of unidentified substrates.
Lung Biology Center, Department of Medicine, University of California-San Francisco, San Francisco, CA 94110, USA.
Chun
C
Chen
Bradford A
BA
Young
Catherine S
CS
Coleman
Anthony E
AE
Pegg
Dean
D
Sheppard
D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019921:Biotinylation; D016466:CHO Cells; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D039001:Integrin alpha Chains / Q000737:chemistry* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D011073:Polyamines / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D003598:Cytoskeletal Proteins; D005982:Glutathione Transferase; D039001:Integrin alpha Chains; D008024:Ligands; D051419:Paxillin; D010750:Phosphoproteins; D011073:Polyamines; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000099228:Diamine N-Acetyltransferase; C496061:PXN protein, human; C084613:integrin alpha9