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.

DOI: 10.1242/jcs.024620

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@article{Kanzaki2008InvolvementOT, title={Involvement of the nectin-afadin complex in PDGF-induced cell survival.}, author={Noriyuki Kanzaki and Hisakazu Ogita and Hitomi Komura and Misa Ozaki and Yasuhisa Sakamoto and Takashi Majima and Takeshi Ijuin and Tadaomi Takenawa and Yoshimi Takai}, journal={Journal of cell science}, year={2008}, volume={121 Pt 12}, pages={2008-17} }