Nesprin-2 interacts with {alpha}-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 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.
Neumann
Sascha
S
Institute of Biochemistry I, Medical Faculty, Center for Molecular Medicine, University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases, 50931 Cologne, Germany.
Schneider
Maria
M
Daugherty
Rebecca L
RL
Gottardi
Cara J
CJ
Eming
Sabine A
SA
Beijer
Asa
A
Noegel
Angelika A
AA
Karakesisoglou
Iakowos
I
D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002522:Chlorocebus aethiops; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C485904:SYNE2 protein, human; D051153:Wnt Proteins; D051178:alpha Catenin; D051176:beta Catenin
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