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Identification of an emerin–β-catenin complex in the heart important for intercalated disc architecture and β-catenin localisation

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Abstract

How mutations in the protein emerin lead to the cardiomyopathy associated with X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is unclear. We identified emerin at the adherens junction of the intercalated disc, where it co-localised with the catenin family of proteins. Emerin bound to wild type β-catenin both in vivo and in vitro. Mutating the GSK3β phosphorylation sites on β-catenin abolished this binding. Wild type but not mutant forms of emerin associated with X-EDMD were able to reduce β-catenin protein levels. Cardiomyocytes from emerin-null mice hearts exhibited erroneous β-catenin distribution and intercalated disc architecture. Treatment of wild type cardiomyocytes with phenylephrine, which inactivates GSK3β, redistributed emerin and β-catenin. Emerin was identified as a direct target of GSK3β activity since exogenous expression of GSK3β reduced emerin levels at the nuclear envelope. We propose that perturbation to or total loss of the emerin–β-catenin complex compromises both intercalated disc function and β-catenin signalling in cardiomyocytes.

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Acknowledgements

Matthew Wheeler was supported by a BHF grant awarded to Juliet Ellis (PG/06/062/20926). We thank Pauline Bennett for help in analysing our EM images, Colin Stewart for the Emd −/y mice and Peter Zammit for critically reading the manuscript.

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Authors and Affiliations

  1. The Randall Division of Cell and Molecular Biophysics, King’s College London, New Hunts House, Guy’s Campus, London, SE1 1UL, UK

    Matthew A. Wheeler & Juliet A. Ellis

  2. Centre for Ultrastructural Imaging, King’s College London, New Hunt’s House, Guy’s Campus, London, SE1 1UL, UK

    Alice Warley

  3. Division of Genetics and Molecular Medicine, Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, SE1 9RT, UK

    Roland G. Roberts

  4. The Randall Division of Cell and Molecular Biophysics and Cardiovascular Division, King’s College London, New Hunts House, Guy’s Campus, London, SE1 1UL, UK

    Elisabeth Ehler

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  1. Matthew A. Wheeler
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Correspondence to Matthew A. Wheeler.

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Wheeler, M.A., Warley, A., Roberts, R.G. et al. Identification of an emerin–β-catenin complex in the heart important for intercalated disc architecture and β-catenin localisation. Cell. Mol. Life Sci. 67, 781–796 (2010). https://doi.org/10.1007/s00018-009-0219-8

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