Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes
Intercalated discs (ICDs), which connect adjacent cardiomyocytes, are composed of desmosomes, adherens junctions (AJs) and gap junctions (GJs). Previous data demonstrated that adrenergic signaling enhances cardiac myocyte cohesion, referred to as positive adhesiotropy, via PKA-mediated phosphorylati...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00430/full |
| _version_ | 1818547719511212032 |
|---|---|
| author | Sunil Yeruva Ellen Kempf Desalegn Tadesse Egu Heinrich Flaswinkel Daniela Kugelmann Jens Waschke |
| author_facet | Sunil Yeruva Ellen Kempf Desalegn Tadesse Egu Heinrich Flaswinkel Daniela Kugelmann Jens Waschke |
| author_sort | Sunil Yeruva |
| collection | DOAJ |
| description | Intercalated discs (ICDs), which connect adjacent cardiomyocytes, are composed of desmosomes, adherens junctions (AJs) and gap junctions (GJs). Previous data demonstrated that adrenergic signaling enhances cardiac myocyte cohesion, referred to as positive adhesiotropy, via PKA-mediated phosphorylation of plakoglobin (PG). However, it was unclear whether positive adhesiotropy caused ultrastructural modifications of ICDs. Therefore, we further investigated the role of PG in adrenergic signaling-mediated ultrastructural changes in the ICD of cardiomyocytes. Quantitative transmission electron microscopy (TEM) analysis of ICD demonstrated that cAMP elevation caused significant elongation of area composita and thickening of the ICD plaque, paralleled by enhanced cardiomyocyte cohesion, in WT but not PG-deficient cardiomyocytes. STED microscopy analysis supported that cAMP elevation ex vivo enhanced overlap of desmoglein-2 (Dsg2) and N-cadherin (N-cad) staining in ICDs of WT but not PG-deficient cardiomyocytes. For dynamic analyses, we utilized HL-1 cardiomyocytes, in which cAMP elevation induced translocation of Dsg2 and PG but not of N-cad to cell junctions. Nevertheless, depletion of N-cad but not of Dsg2 resulted in a decrease in basal cell cohesion whereas positive adhesiotropy was abrogated in monolayers depleted for either Dsg2 or N-cad. In the WT mice, ultrastrutural changes observed after cAMP elevation were paralleled by phosphorylation of PG at serine 665. Our data demonstrate that in murine hearts adrenergic signaling enhanced N-cad and Dsg2 in the ICD paralleled by ultrastrutural strengthening of ICDs and that effects induced by positive adhesiotropy were strictly dependent on Pg. |
| first_indexed | 2024-12-12T08:10:30Z |
| format | Article |
| id | doaj.art-d0663833363645b3bf1e7e13a1a676b0 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-12T08:10:30Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-d0663833363645b3bf1e7e13a1a676b02022-12-22T00:31:48ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-05-011110.3389/fphys.2020.00430526845Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine CardiomyocytesSunil Yeruva0Ellen Kempf1Desalegn Tadesse Egu2Heinrich Flaswinkel3Daniela Kugelmann4Jens Waschke5Institute of Anatomy and Cell Biology, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, GermanyInstitute of Anatomy and Cell Biology, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, GermanyInstitute of Anatomy and Cell Biology, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, GermanyBioSysM, Ludwig-Maximilians-Universität Munich, Munich, GermanyInstitute of Anatomy and Cell Biology, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, GermanyInstitute of Anatomy and Cell Biology, Faculty of Medicine, Ludwig-Maximilians-Universität Munich, Munich, GermanyIntercalated discs (ICDs), which connect adjacent cardiomyocytes, are composed of desmosomes, adherens junctions (AJs) and gap junctions (GJs). Previous data demonstrated that adrenergic signaling enhances cardiac myocyte cohesion, referred to as positive adhesiotropy, via PKA-mediated phosphorylation of plakoglobin (PG). However, it was unclear whether positive adhesiotropy caused ultrastructural modifications of ICDs. Therefore, we further investigated the role of PG in adrenergic signaling-mediated ultrastructural changes in the ICD of cardiomyocytes. Quantitative transmission electron microscopy (TEM) analysis of ICD demonstrated that cAMP elevation caused significant elongation of area composita and thickening of the ICD plaque, paralleled by enhanced cardiomyocyte cohesion, in WT but not PG-deficient cardiomyocytes. STED microscopy analysis supported that cAMP elevation ex vivo enhanced overlap of desmoglein-2 (Dsg2) and N-cadherin (N-cad) staining in ICDs of WT but not PG-deficient cardiomyocytes. For dynamic analyses, we utilized HL-1 cardiomyocytes, in which cAMP elevation induced translocation of Dsg2 and PG but not of N-cad to cell junctions. Nevertheless, depletion of N-cad but not of Dsg2 resulted in a decrease in basal cell cohesion whereas positive adhesiotropy was abrogated in monolayers depleted for either Dsg2 or N-cad. In the WT mice, ultrastrutural changes observed after cAMP elevation were paralleled by phosphorylation of PG at serine 665. Our data demonstrate that in murine hearts adrenergic signaling enhanced N-cad and Dsg2 in the ICD paralleled by ultrastrutural strengthening of ICDs and that effects induced by positive adhesiotropy were strictly dependent on Pg.https://www.frontiersin.org/article/10.3389/fphys.2020.00430/fulldesmosomearrhythmogenic cardiomyopathyintercalated discintercellular adhesionpositive adhesiotropy |
| spellingShingle | Sunil Yeruva Ellen Kempf Desalegn Tadesse Egu Heinrich Flaswinkel Daniela Kugelmann Jens Waschke Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes Frontiers in Physiology desmosome arrhythmogenic cardiomyopathy intercalated disc intercellular adhesion positive adhesiotropy |
| title | Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes |
| title_full | Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes |
| title_fullStr | Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes |
| title_full_unstemmed | Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes |
| title_short | Adrenergic Signaling-Induced Ultrastructural Strengthening of Intercalated Discs via Plakoglobin Is Crucial for Positive Adhesiotropy in Murine Cardiomyocytes |
| title_sort | adrenergic signaling induced ultrastructural strengthening of intercalated discs via plakoglobin is crucial for positive adhesiotropy in murine cardiomyocytes |
| topic | desmosome arrhythmogenic cardiomyopathy intercalated disc intercellular adhesion positive adhesiotropy |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00430/full |
| work_keys_str_mv | AT sunilyeruva adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes AT ellenkempf adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes AT desalegntadesseegu adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes AT heinrichflaswinkel adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes AT danielakugelmann adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes AT jenswaschke adrenergicsignalinginducedultrastructuralstrengtheningofintercalateddiscsviaplakoglobiniscrucialforpositiveadhesiotropyinmurinecardiomyocytes |