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

Nesprins and emerin are structural nuclear envelope proteins that tether nuclei to the cytoskeleton. In this work, we identified the cytoskeleton-associated alpha-N/E-catenins as novel nesprin-2-binding partners. The association involves the C termini of nesprin-2 giant and alpha-N/E-catenins. alpha-E/T/N-catenins are known primarily for their roles in cadherin-mediated cell-cell adhesion. Here, we show that, in addition, alpha-catenin forms complexes with nesprin-2 that include beta-catenin and emerin. We demonstrate that the depletion of nesprin-2 reduces both the amount of active beta-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.