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  1. Article ; Online: The N Terminus of Adhesion G Protein–Coupled Receptor GPR126/ADGRG6 as Allosteric Force Integrator

    Jakob Mitgau / Julius Franke / Camilla Schinner / Gabriele Stephan / Sandra Berndt / Dimitris G. Placantonakis / Hermann Kalwa / Volker Spindler / Caroline Wilde / Ines Liebscher

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: The adhesion G protein–coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the receptor an attractive pharmacological target. GPR126 is a mechano- ... ...

    Abstract The adhesion G protein–coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the receptor an attractive pharmacological target. GPR126 is a mechano-sensor that translates the binding of extracellular matrix (ECM) molecules to its N terminus into a metabotropic intracellular signal. To date, the structural requirements and the character of the forces needed for this ECM-mediated receptor activation are largely unknown. In this study, we provide this information by combining classic second-messenger detection with single-cell atomic force microscopy. We established a monoclonal antibody targeting the N terminus to stimulate GPR126 and compared it to the activation through its known ECM ligands, collagen IV and laminin 211. As each ligand uses a distinct mode of action, the N terminus can be regarded as an allosteric module that can fine-tune receptor activation in a context-specific manner.
    Keywords adhesion GPCR ; mechano-activation ; signal transduction ; allosteric modulator ; activating antibody ; extracellular matrix ligand ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Cardiomyocyte adhesion and hyperadhesion differentially require ERK1/2 and plakoglobin

    Maria Shoykhet / Sebastian Trenz / Ellen Kempf / Tatjana Williams / Brenda Gerull / Camilla Schinner / Sunil Yeruva / Jens Waschke

    JCI Insight, Vol 5, Iss

    2020  Volume 18

    Abstract: Arrhythmogenic cardiomyopathy (AC) is a heart disease often caused by mutations in genes coding for desmosomal proteins, including desmoglein-2 (DSG2), plakoglobin (PG), and desmoplakin (DP). Therapy is based on symptoms and limiting arrhythmia, because ... ...

    Abstract Arrhythmogenic cardiomyopathy (AC) is a heart disease often caused by mutations in genes coding for desmosomal proteins, including desmoglein-2 (DSG2), plakoglobin (PG), and desmoplakin (DP). Therapy is based on symptoms and limiting arrhythmia, because the mechanisms by which desmosomal components control cardiomyocyte function are largely unknown. A new paradigm could be to stabilize desmosomal cardiomyocyte adhesion and hyperadhesion, which renders desmosomal adhesion independent from Ca2+. Here, we further characterized the mechanisms behind enhanced cardiomyocyte adhesion and hyperadhesion. Dissociation assays performed in HL-1 cells and murine ventricular cardiac slice cultures allowed us to define a set of signaling pathways regulating cardiomyocyte adhesion under basal and hyperadhesive conditions. Adrenergic signaling, activation of PKC, and inhibition of p38MAPK enhanced cardiomyocyte adhesion, referred to as positive adhesiotropy, and induced hyperadhesion. Activation of ERK1/2 paralleled positive adhesiotropy, whereas adrenergic signaling induced PG phosphorylation at S665 under both basal and hyperadhesive conditions. Adrenergic signaling and p38MAPK inhibition recruited DSG2 to cell junctions. In PG-deficient mice with an AC phenotype, only PKC activation and p38MAPK inhibition enhanced cardiomyocyte adhesion. Our results demonstrate that cardiomyocyte adhesion can be stabilized by different signaling mechanisms, which are in part offset in PG-deficient AC.
    Keywords Cardiology ; Medicine ; R
    Subject code 572
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro

    Carola Fischer / Hendrik Milting / Evelyn Fein / Elisabeth Reiser / Kun Lu / Thomas Seidel / Camilla Schinner / Thomas Schwarzmayr / Rene Schramm / Roland Tomasi / Britta Husse / Xiaochun Cao-Ehlker / Ulrich Pohl / Andreas Dendorfer

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for ... ...

    Abstract Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for evaluation of drug safety, as exemplified for drugs interfering with cardiomyocyte repolarization.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Publisher Correction

    Carola Fischer / Hendrik Milting / Evelyn Fein / Elisabeth Reiser / Kun Lu / Thomas Seidel / Camilla Schinner / Thomas Schwarzmayr / Rene Schramm / Roland Tomasi / Britta Husse / Xiaochun Cao-Ehlker / Ulrich Pohl / Andreas Dendorfer

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro

    2019  Volume 1

    Abstract: The original version of this Article incorrectly acknowledged Elisabeth Reiser and Rene Schramm as a corresponding author. This has now been corrected in both the PDF and HTML versions of the Article. ...

    Abstract The original version of this Article incorrectly acknowledged Elisabeth Reiser and Rene Schramm as a corresponding author. This has now been corrected in both the PDF and HTML versions of the Article.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  5. Article ; Online: Publisher Correction

    Carola Fischer / Hendrik Milting / Evelyn Fein / Elisabeth Reiser / Kun Lu / Thomas Seidel / Camilla Schinner / Thomas Schwarzmayr / Rene Schramm / Roland Tomasi / Britta Husse / Xiaochun Cao-Ehlker / Ulrich Pohl / Andreas Dendorfer

    Nature Communications, Vol 10, Iss 1, Pp 1-

    Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro

    2019  Volume 1

    Abstract: The original version of this Article incorrectly acknowledged Elisabeth Reiser and Rene Schramm as a corresponding author. This has now been corrected in both the PDF and HTML versions of the Article. ...

    Abstract The original version of this Article incorrectly acknowledged Elisabeth Reiser and Rene Schramm as a corresponding author. This has now been corrected in both the PDF and HTML versions of the Article.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro

    Carola Fischer / Hendrik Milting / Evelyn Fein / Elisabeth Reiser / Kun Lu / Thomas Seidel / Camilla Schinner / Thomas Schwarzmayr / Rene Schramm / Roland Tomasi / Britta Husse / Xiaochun Cao-Ehlker / Ulrich Pohl / Andreas Dendorfer

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for ... ...

    Abstract Myocardial tissue undergoes steady functional decline when cultured in vitro. Here, the authors report a protocol for culture of human cardiac slices that allows maintenance of contractility for up to four months, and show that the model is suitable for evaluation of drug safety, as exemplified for drugs interfering with cardiomyocyte repolarization.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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