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

Matthew A Wheeler, Alice Warley, Roland G Roberts, Elisabeth Ehler, Juliet A Ellis

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@kcl.ac.uk

Cellular and molecular life sciences : CMLS 2010 Mar

filter terms:

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 beta-catenin both in vivo and in vitro. Mutating the GSK3beta phosphorylation sites on beta-catenin abolished this binding. Wild type but not mutant forms of emerin associated with X-EDMD were able to reduce beta-catenin protein levels. Cardiomyocytes from emerin-null mice hearts exhibited erroneous beta-catenin distribution and intercalated disc architecture. Treatment of wild type cardiomyocytes with phenylephrine, which inactivates GSK3beta, redistributed emerin and beta-catenin. Emerin was identified as a direct target of GSK3beta activity since exogenous expression of GSK3beta reduced emerin levels at the nuclear envelope. We propose that perturbation to or total loss of the emerin-beta-catenin complex compromises both intercalated disc function and beta-catenin signalling in cardiomyocytes.

Citation

Matthew A Wheeler, Alice Warley, Roland G Roberts, Elisabeth Ehler, Juliet A Ellis. Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation. Cellular and molecular life sciences : CMLS. 2010 Mar;67(5):781-96