At the heart of inter- and intracellular signaling: the intercalated disc

Manring, Heather R.; Dorn, Lisa E.; Ex-Willey, Aidan; Accornero, Federica; Ackermann, Maegen A.

doi:10.1007/s12551-018-0430-7

Cited by 31 publications

(35 citation statements)

References 123 publications

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“…Interestingly, stronger contractions of the cell scaffolds were observed for the treatment groups. Such contractions are an indication of intercalated discs, which are composed of gap junctions, adherent junctions, and desmosomes between the cardiomyocytes [67]. This was confirmed using TEM, showing the presence of the different structures ( Figure 2F).…”

Section: Cardioprotectionsupporting

confidence: 55%

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

Jansman

Hosta‐Rigau

2019

Catalysts

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Nanoparticulate materials displaying enzyme-like properties, so-called nanozymes, are explored as substitutes for natural enzymes in several industrial, energy-related, and biomedical applications. Outstanding high stability, enhanced catalytic activities, low cost, and availability at industrial scale are some of the fascinating features of nanozymes. Furthermore, nanozymes can also be equipped with the unique attributes of nanomaterials such as magnetic or optical properties. Due to the impressive development of nanozymes during the last decade, their potential in the context of tissue engineering and regenerative medicine also started to be explored. To highlight the progress, in this review, we discuss the two most representative nanozymes, namely, cerium- and iron-oxide nanomaterials, since they are the most widely studied. Special focus is placed on their applications ranging from cardioprotection to therapeutic angiogenesis, bone tissue engineering, and wound healing. Finally, current challenges and future directions are discussed.

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Section: Cardioprotectionsupporting

confidence: 55%

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

Jansman

Hosta‐Rigau

2019

Catalysts

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“…The intercalated disc is formed from the juxtaposition of the sarcolemma membranes from adjacent cardiomyocytes and enables the cells to be mechanically and electrically coupled together [ 37 ]. It has a complex inter-digitated ‘plicate’ structure that ensures the inter-cellular connections are both close and continuous.…”

Section: The Nav Channel β-Subunits As Cell-adhesion Moleculesmentioning

confidence: 99%

Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels

2020

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Voltage-gated sodium (Nav) channels drive the rising phase of the action potential, essential for electrical signalling in nerves and muscles. The Nav channel α-subunit contains the ion-selective pore. In the cardiomyocyte, Nav1.5 is the main Nav channel α-subunit isoform, with a smaller expression of neuronal Nav channels. Four distinct regulatory β-subunits (β1–4) bind to the Nav channel α-subunits. Previous work has emphasised the β-subunits as direct Nav channel gating modulators. However, there is now increasing appreciation of additional roles played by these subunits. In this review, we focus on β-subunits as homophilic and heterophilic cell-adhesion molecules and the implications for cardiomyocyte function. Based on recent cryogenic electron microscopy (cryo-EM) data, we suggest that the β-subunits interact with Nav1.5 in a different way from their binding to other Nav channel isoforms. We believe this feature may facilitate trans-cell-adhesion between β1-associated Nav1.5 subunits on the intercalated disc and promote ephaptic conduction between cardiomyocytes.

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“…It has been reported that γ-catenin is rapidly degraded when expressed in a fibroblast model system in the absence of interactions with either desmoglein or desmocollin (Kowalczyk et al, 1994). As a member of the armadillo family of proteins and a paralog of β-catenin, γ-catenin also participates in cell signaling in addition to its role as a structural protein (Manring et al, 2018). The protein level of γ-catenin was dramatically decreased during CVB3 infection and no significant amount of cleaved products was observed in our Western blot analysis.…”

Section: Discussionmentioning

confidence: 63%

Cleavage of Desmosomal Cadherins Promotes γ-Catenin Degradation and Benefits Wnt Signaling in Coxsackievirus B3-Induced Destruction of Cardiomyocytes

et al. 2020

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Coxsackievirus B3 (CVB3) is the primary etiologic agent of viral myocarditis, a major heart disease that occurs predominantly in children and young adolescents. In the heart, intercalated disks (ICD) are important structural formations that connect adjacent cardiomyocytes to maintain cardiac architecture and mediate signal communication. Deficiency in ICD components, such as desmosome proteins, leads to heart dysfunction. γ-catenin, a component protein of desmosomes, normally binds directly to desmocollin-2 and desmoglein-2. In this study, we found that CVB3 infection downregulated γ-catenin at the protein level but not the mRNA level in mouse HL-1 cardiomyocytes. We further found that this reduction of γ-catenin protein is a result of ubiquitin proteasome-mediated degradation, since the addition of proteasome inhibitor MG132 inhibited γ-catenin downregulation. In addition, we found that desmocollin-2 and desmoglein-2 were cleaved by both viral protease 3C and virus-activated cellular caspase, respectively. These cleavages led to the release of bound γ-catenin from the desmosome into the cytosol, resulting in rapid degradation of γ-catenin. Since γ-catenin shares high sequence homology with β-catenin in binding the TCF/LEF transcription factor, we further studied the effect of γ-catenin degradation on Wnt/β-catenin signaling. Luciferase assay showed that γ-catenin expression inhibited Wnt/β-catenin signaling. This finding was substantiated by qPCR to show that overexpression of γ-catenin downregulated transcription of Wnt signal target genes, c-myc and MMP9, while silencing γ-catenin upregulated these target genes. Finally, we demonstrated that γcatenin expression inhibited CVB3 replication. In search for the underlying mechanism, we found that silencing γ-catenin caused down-regulation of interferon-β and its stimulated antiviral genes MDA5, MAVS, and ISG15. Taken together, our results indicate, for the first time, that CVB3 infection causes cardiomyocyte death through, at least in

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At the heart of inter- and intracellular signaling: the intercalated disc

Cited by 31 publications

References 123 publications

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

Cerium- and Iron-Oxide-Based Nanozymes in Tissue Engineering and Regenerative Medicine

Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels

Cleavage of Desmosomal Cadherins Promotes γ-Catenin Degradation and Benefits Wnt Signaling in Coxsackievirus B3-Induced Destruction of Cardiomyocytes

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