Con-nectin' adhesion and survival

Nectins, which are a family of immunoglobulin-like transmembrane proteins, participate in intercellular adhesion, and help to form tight junctions (TJs) and adherens junctions (AJs). The cytoplasmic region of nectins is connected to the cytoskeleton by the actin-binding protein afadin. Mice that lack afadin die during embryogenesis and have disorganised TJs and AJs; however, it was not previously known whether developmental mechanisms such as apoptosis are affected by the absence of afadin. Yoshimi Takai and colleagues (p. 2008) now show that embryoid bodies that are derived from afadin^–/– embryonic stem cells contain many more apoptotic cells than those that are derived from wild-type cells. In addition, apoptosis (whether induced by the intrinsic or extrinsic pathway) is stimulated in NIH3T3 cells when afadin or nectin-3 is knocked down. Using the same cell line, the authors show that PDGF-dependent signalling through PI3K-Akt – a key pro-survival pathway – is substantially inhibited in the absence of afadin or nectin-3. Moreover, the nectin-afadin complex associates with the PDGF receptor at cell-cell boundaries. The authors conclude that the nectin-3–afadin complex has a role in PDGF-induced cell survival.