scholarly journals Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin-43-containing gap junctions in cardiac myocytes

2014 ◽  
Vol 127 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
A. E. Zemljic-Harpf ◽  
J. C. Godoy ◽  
O. Platoshyn ◽  
E. K. Asfaw ◽  
A. R. Busija ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cardiac Myocytes ◽  
Connexin 43 ◽  
Zonula Occludens ◽  
Zonula Occludens 1

scholarly journals Vinculin directly binds zonula occludens-1 and is essential for stabilizing connexin-43-containing gap junctions in cardiac myocytes

Development ◽  
2014 ◽  
Vol 141 (7) ◽  
pp. e708-e708
Author(s):  
A. E. Zemljic-Harpf ◽  
J. C. Godoy ◽  
O. Platoshyn ◽  
E. K. Asfaw ◽  
A. R. Busija ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cardiac Myocytes ◽  
Connexin 43 ◽  
Zonula Occludens ◽  
Zonula Occludens 1

Does zonula occludens 1 play a role in remodelling of connexin43 gap junctions in the failing human ventricle?

2006 ◽  
Vol 40 (6) ◽  
pp. 948-949
Author(s):  
Alexandra F. Bruce ◽  
Stephen Rothery ◽  
Emmanuel Dupont ◽  
Nicholas J. Severs
Keyword(s):  
Gap Junctions ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
Connexin43 Gap Junctions

scholarly journals Dysfunction of mitochondria and deformed gap junctions in the heart of IL-18-deficient mice

2016 ◽  
Vol 311 (2) ◽  
pp. H313-H325 ◽  
Author(s):  
Wen Li ◽  
Denan Jin ◽  
Masaki Hata ◽  
Shinji Takai ◽  
Kyosuke Yamanishi ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Cardiac Myocytes ◽  
Proinflammatory Cytokine ◽  
Connexin 43 ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
Morphological Observation ◽  
Mouse Heart ◽  
Endurance Running ◽  
Heart Abnormalities

Interleukin-18 (IL-18) was discovered as an interferon-γ-inducing factor and has been regarded as a proinflammatory cytokine. However, IL-18 is ubiquitously expressed both in immune/inflammatory cells and in nonimmune cells, and its biological roles have not been sufficiently elucidated. Here, we demonstrate that IL-18-deficient [IL-18 knockout (KO)] mice have heart abnormalities that may be related to impaired autophagy. In endurance running tests, IL-18KO mice ran significantly shorter distances compared with wild-type (WT) mice. Echocardiographs indicated disability in the systolic and diastolic functions of the IL-18KO mouse heart. Immunostaining of connexin 43 showed heterogeneous localization of gap junctions in the lateral membranes of the IL-18KO cardiac myocytes. Western blotting analysis revealed decreased phosphorylated connexin 43 in the IL-18KO heart. Electron microscopy revealed unusual localization of intercalated disks, swollen or damaged mitochondria, and broad, indistinct Z-lines in the IL-18KO heart. In accordance with the morphological observation, mitochondrial respiratory function, including that of complexes I and IV, was impaired, and production of reactive oxygen species was augmented in IL-18KO hearts. Notably, levels of LC3-II were markedly lower in the IL-18KO hearts than in WT hearts. In the culture of cardiac myocytes of IL-18KO neonates, exogenous IL-18 upregulated LC3-II and increased the number of intact mitochondria with high mitochondrial membrane potential. These results indicated that IL-18 has roles apart from those as a proinflammatory cytokine in cardiac myocytes and suggested that IL-18 contributes to the homeostatic maintenance of mitochondrial function and gap-junction turnover in cardiac myocytes, possibly by upregulating autophagy.

scholarly journals ZO-1 determines adherens and gap junction localization at intercalated disks

2011 ◽  
Vol 300 (2) ◽  
pp. H583-H594 ◽  
Author(s):  
Joseph A. Palatinus ◽  
Michael P. O'Quinn ◽  
Ralph J. Barker ◽  
Brett S. Harris ◽  
Jane Jourdan ◽  
...  
Keyword(s):  
Connexin 43 ◽  
Ventricular Myocytes ◽  
Dominant Negative ◽  
Cell Junction ◽  
Disease States ◽  
Zonula Occludens ◽  
Zonula Occludens 1 ◽  
Intercalated Disks

The disruption of the spatial order of electromechanical junctions at myocyte-intercalated disks (ICDs) is a poorly understood characteristic of many cardiac disease states. Here, in vitro and in vivo evidence is provided that zonula occludens-1 (ZO-1) regulates the organization of gap junctions (GJs) and adherens junctions (AJs) at ICDs. We investigated the contribution of ZO-1 to cell-cell junction localization by expressing a dominant-negative ZO-1 construct (DN-ZO-1) in rat ventricular myocytes (VMs). The expression of DN-ZO-1 in cultured neonatal VMs for 72 h reduced the interaction of ZO-1 and N-cadherin, as assayed by colocalization and coimmunoprecipitation, prompting cytoplasmic internalization of AJ and GJ proteins. DN-ZO-1 expression in adult VMs in vivo also reduced N-cadherin colocalization with ZO-1, a phenomenon not observed when the connexin-43 (Cx43)-ZO-1 interaction was disrupted using a mimetic of the ZO-1-binding ligand from Cx43. DN-ZO-1-infected VMs demonstrated large GJs at the ICD periphery and showed a loss of focal ZO-1 concentrations along plaque edges facing the disk interior. Additionally, there was breakdown of the characteristic ICD pattern of small interior and large peripheral GJs. Continuous DN-ZO-1 expression in VMs over postnatal development reduced ICD-associated Cx43 GJs and increased lateralized and cytoplasmic Cx43. We conclude that ZO-1 regulation of GJ localization is via an association with the N-cadherin multiprotein complex and that this is a key determinant of stable localization of both AJs and GJs at the ICD.

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