PINCHing together integrins and signaling

Integrin-mediated adhesion and intracellular signaling by JNK are both required for proper cell migration, but it isn't clear what factors integrate the two information systems. Kadrmas et al. show on page 1019 that the integrin effector protein PINCH provides such a link during Drosophila dorsal closure, which involves coordinated migration and adhesion of epithelial sheets. PINCH interacts with integrin-linked kinase and with Nck2, which is involved in regulation of JNK pathway through MAP4 kinase, making it a likely candidate for bridging the two information sources. Using a series of maternal and zygotic mutants, the team found that PINCH was required for proper dorsal closure and that it acted as a negative regulator of the JNK cascade. Moreover, Kadrmas et al. affinity purified a novel PINCH partner RSU-1, a previously identified suppressor of ras-mediated transformation in mammalian cells. PINCH and RSU-1 stabilized one another and were required for proper JNK activity. Exactly where in the process of dorsal closure PINCH and RSU-1 are required is the subject of the group's future work. But the current study does imply that integrin-associated junctional complexes may act as signal coordination points, and that JNK signaling must be finely tuned for proper zipping of the epithelial sheet.