Portal de investigação
EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Martins Marques, T
- Catarino, S
- Gonçalves, A
- Miranda-Silva, D
- Gonçalves, L
- Antunes, P
- Coutinho, G
- Moreira, AL
- Girao, H
Unidades de investigação
Abstract
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.
Dados da publicação
- ISSN/ISSNe:
- 0009-7330, 1524-4571
- Tipo:
- Article
- Páginas:
- 97-113
- Link para outro recurso:
- www.scopus.com
Circulation Research Lippincott Williams and Wilkins Ltd.
Citações Recebidas na Web of Science: 39
Citações Recebidas na Scopus: 42
Documentos
- Não há documentos
Filiações
Keywords
- connexin43; gap junctions; heart failure; myocardial infarction; ubiquitination
Campos de estudo
Financiamento
Proyectos asociados
Cardiac Remodelling and “Recovery” in Pregnancy as a Model to Understand the Mechanisms of CV Diseases.
Investigador Principal: Inês Maria Falcão Sousa Pires Marques
Estudo Observacional Académico (PERIMYR) . SP Cardiologia . 2019
Citar a publicação
Martins T,Catarino S,Gonçalves A,Miranda D,Gonçalves L,Antunes P,Coutinho G,Moreira AL,Pires IF,Girao H. EHD1 Modulates Cx43 Gap Junction Remodeling Associated With Cardiac Diseases. Circ.Res. 2020. 126. (10):p. 97-113. IF:17,367. (1).
