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

被引:58
作者
Neumann, Sascha [1 ]
Schneider, Maria [1 ]
Daugherty, Rebecca L. [3 ]
Gottardi, Cara J. [3 ]
Eming, Sabine A. [2 ]
Beijer, Asa [1 ]
Noegel, Angelika A. [1 ]
Karakesisoglou, Iakowos [4 ]
机构
[1] Univ Cologne, Fac Med, Inst Biochem 1, Ctr Mol Med, D-50931 Cologne, Germany
[2] Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany
[3] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA
[4] Univ Durham, Sch Biol & Biomed Sci, Dept Biol Sci, Durham DH1 3LE, England
基金
美国国家卫生研究院;
关键词
BETA-CATENIN; MEMBRANE PROTEIN; N-CATENIN; EMERIN; CELLS; LOCALIZATION; ACTIVATION; ANCHORAGE; ISOFORMS; DOMAINS;
D O I
10.1074/jbc.M110.119651
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:34932 / 34938
页数:7
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