EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases.

Circulation Research
Tania Martins-MarquesHenrique Girão

Abstract

Efficient communication between heart cells is vital to ensure the anisotropic propagation of electrical impulses, a function mainly accomplished by gap junctions (GJ) composed of Cx43 (connexin 43). Although the molecular mechanisms remain unclear, altered distribution and function of gap junctions have been associated with acute myocardial infarction and heart failure. A recent proteomic study from our laboratory identified EHD1 (Eps15 [endocytic adaptor epidermal growth factor receptor substrate 15] homology domain-containing protein 1) as a novel interactor of Cx43 in the heart. In the present work, we demonstrate that knockdown of EHD1 impaired the internalization of Cx43, preserving gap junction-intercellular coupling in cardiomyocytes. Interaction of Cx43 with EHD1 was mediated by Eps15 and promoted by phosphorylation and ubiquitination of Cx43. Overexpression of wild-type EHD1 accelerated internalization of Cx43 and exacerbated ischemia-induced lateralization of Cx43 in isolated adult cardiomyocytes. In addition, we show that EHDs associate with Cx43 in human and murine failing hearts. Overall, we identified EHDs as novel regulators of endocytic trafficking of Cx43, participating in the pathological remodeling of gap ju...Continue Reading

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Citations

Aug 28, 2020·Biomolecules·Olga M RusieckaBrenda R Kwak
Oct 25, 2020·Life Science Alliance·Tania Martins-MarquesHenrique Girao
Jan 28, 2021·International Journal of Molecular Sciences·Kerstin BoenglerRainer Schulz
Jan 2, 2021·International Journal of Molecular Sciences·Katarina AndelovaNarcis Tribulova
Nov 4, 2020·Trends in Molecular Medicine·Tania Martins-MarquesHenrique Girao
Mar 3, 2021·Revista Portuguesa De Cardiologia : Orgão Oficial Da Sociedade Portuguesa De Cardiologia = Portuguese Journal of Cardiology : an Official Journal of the Portuguese Society of Cardiology·Henrique Girão, Tania Martins-Marques
Mar 23, 2021·Frontiers in Cardiovascular Medicine·Beijian ZhangJunbo Ge
Apr 24, 2021·Free Radical Biology & Medicine·Tania Martins-MarquesHenrique Girao
Sep 9, 2021·Biology Open·Tania Martins-Marques

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Methods Mentioned

BETA
ubiquitination
immunoprecipitation
confocal microscopy
fluorescence microscopy
transfection
pull down
PMA
biopsies
coimmunoprecipitation

Software Mentioned

ImageJ
GraphPad Prism
GraphPad

Related Concepts