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.
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 beta1, beta3, beta4, (alpha)2, (alpha)3, (alpha)5, (alpha)6 and provide the first report of Transmembrane 4 Superfamily association with the (alpha)6beta4 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.
Division of Haematology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, Australia.
P M
PM
Sincock
S
S
Fitter
R G
RG
Parton
M C
MC
Berndt
J R
JR
Gamble
L K
LK
Ashman
D015703:Antigens, CD / Q000032:analysis* / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure*; D002465:Cell Movement; D002478:Cells, Cultured; D004705:Endocytosis; D011992:Endosomes / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D016023:Integrins / Q000032:analysis; D007365:Intercellular Junctions / Q000502:physiology / Q000648:ultrastructure; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D018919:Neovascularization, Physiologic; D010980:Platelet Membrane Glycoproteins / Q000032:analysis; D011990:Receptors, Transferrin / Q000032:analysis; D060185:Tetraspanin 24; D060149:Tetraspanin 30; D014471:Umbilical Veins
D015703:Antigens, CD; C554715:CD151 protein, human; C554586:CD63 protein, human; D016023:Integrins; D010980:Platelet Membrane Glycoproteins; D011990:Receptors, Transferrin; D060185:Tetraspanin 24; D060149:Tetraspanin 30