PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function

Paul M. Sincock, Stephen Fitter, Robert G. Parton, Michael C. Berndt, Jennifer R. Gamble, Leonie K. Ashman

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148 Citations (Scopus)

Abstract

The Transmembrane 4 Superfamily member, PETA-3/CD151, is ubiquitously expressed by endothelial cells in vivo. In cultured human umbilical vein endothelial cells PETA-3 is present on the plasma membrane and predominantly localises to regions of cell-cell contact. Additionally, this protein is abundant within an intracellular compartment which accounts for up to 66% of the total PETA-3 expressed. Intracellular PETA-3 showed colocalisation with transferrin receptor and CD63 suggesting an endosomal/lysosomal localisation which was supported by immuno-electronmicroscopy studies. Co-immunoprecipitation experiments investigating possible interactions of PETA-3 with other molecules demonstrated associations with several integrin chains including β1, β3, β4, α2, α3, α5, α6 and provide the first report of Transmembrane 4 Superfamily association with the α6β4 integrin. Using 2-colour confocal microscopy, we demonstrated similar localisation of PETA-3 and integrin chains within cytoplasmic vesicles and endothelial cell junctions. In order to assess the functional implications of PETA-3/integrin associations, the effect of anti-PETA-3 antibodies on endothelial function was examined. Anti-PETA-3 mAb inhibited endothelial cell migration and modulated in vitro angiogenesis, but had no detectable effect on neutrophil transendothelial migration. The broad range of integrin associations and the presence of PETA-3 with integrins both on the plasma membrane and within intracellular vesicles, suggests a primary role for PETA-3 in regulating integrin trafficking and/or function.

Original languageEnglish
Pages (from-to)833-844
Number of pages12
JournalJournal of cell science
Volume112
Issue number6
Publication statusPublished - 26 Apr 1999
Externally publishedYes

Keywords

  • Angiogenesis
  • Cell migration
  • Integrin
  • Multi-protein complex
  • Protein trafficking
  • TM4SF

ASJC Scopus subject areas

  • Cell Biology

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