Nesprin-2 Interacts with α-Catenin and Regulates Wnt Signaling at the Nuclear Envelope

Abstract

Nesprins and emerin are structural nuclear envelope proteins that tether nuclei to the cytoskeleton. In this work, we identified the cytoskeleton-associated α-N/E-catenins as novel nesprin-2-binding partners. The association involves the C termini of nesprin-2 giant and α-N/E-catenins. α-E/T/N-catenins are known primarily for their roles in cadherin-mediated cell-cell adhesion. Here, we show that, in addition, α-catenin forms complexes with nesprin-2 that include β-catenin and emerin. We demonstrate that the depletion of nesprin-2 reduces both the amount of active β-catenin inside the nucleus and T-cell factor/lymphoid-enhancing factor-dependent transcription. Taken together, these findings suggest novel nesprin-2 functions in cellular signaling. Moreover, we propose that, in contrast to emerin, nesprin-2 is a positive regulator of the Wnt signaling pathway.