Involvement of the nectin-afadin complex in PDGF-induced cell survival.
The nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJs) and tight junctions (TJs). Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, whereas afadin is an intracellular nectin-binding protein that connects nectins to the cadherin-catenin system at AJs and to the claudin-zona-occludens (ZO) protein system at TJs. Afadin(-/-) mice show embryonic lethality, resulting from impaired migration and improper differentiation of cells due to disorganization of cell-cell junctions during gastrulation. However, it remains to be elucidated whether disruption of afadin affects apoptosis. In the present study, we first found that embryoid bodies derived from afadin-knockout embryonic stem (ES) cells contained many more apoptotic cells than those derived from wild-type ES cells. We also revealed that apoptosis induced by serum starvation or Fas-ligand stimulation was increased in cultured NIH3T3 cells when afadin or nectin-3 was knocked down. The nectin-afadin complex was involved in the platelet-derived growth factor (PDGF)-induced activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling for cell survival. This complex was associated with PDGF receptor on the plasma membrane at cell-cell adhesion sites. Thus, the nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway.
Kanzaki
Noriyuki
N
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka, Japan.
Ogita
Hisakazu
H
Komura
Hitomi
H
Ozaki
Misa
M
Sakamoto
Yasuhisa
Y
Majima
Takashi
T
Ijuin
Takeshi
T
Takenawa
Tadaomi
T
Takai
Yoshimi
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D000075983:Nectins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D053222:Fas Ligand Protein; D008840:Microfilament Proteins; C000619014:NECTIN3 protein, human; C000619017:Nectin3 protein, mouse; D000075983:Nectins; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; C108835:afadin; D019869:Phosphatidylinositol 3-Kinases