Related Experiment Video
Updated: Dec 27, 2025

Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases
Tania Martins-Marques1,2,3, Steve Catarino1,2,3, Alexandre Gonçalves4
1From the Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine (T.M.-M., S.C., L.C., P.A., G.C., H.G.), University of Coimbra, Portugal.
Rationale:
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.
Objective:
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.
Methods And Results:
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.
Conclusions:
Overall, we identified EHDs as novel regulators of endocytic trafficking of Cx43, participating in the pathological remodeling of gap junctions, paving the way to innovative therapeutic strategies aiming at preserving intercellular communication in the heart.
Related Concept Videos
Gap Junctions
Gap Junctions
Cardiomyopathy III: Hypertrophic Cardiomyopathy
Heart Failure II: Pathophysiology
Mechanism of Cardiac Arrhythmias
Cardiomyopathy II: Dilated Cardiomyopathy

