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  1. Artikel ; Online: The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function

    Kathleen J. Green / Carien M. Niessen / Matthias Rübsam / Bethany E. Perez White / Joshua A. Broussard

    Frontiers in Cell and Developmental Biology, Vol

    2022  Band 10

    Abstract: While classic cadherin-actin connections in adherens junctions (AJs) have ancient origins, intermediate filament (IF) linkages with desmosomal cadherins arose in vertebrate organisms. In this mini-review, we discuss how overlaying the IF-desmosome ... ...

    Abstract While classic cadherin-actin connections in adherens junctions (AJs) have ancient origins, intermediate filament (IF) linkages with desmosomal cadherins arose in vertebrate organisms. In this mini-review, we discuss how overlaying the IF-desmosome network onto the existing cadherin-actin network provided new opportunities to coordinate tissue mechanics with the positioning and function of chemical signaling mediators in the ErbB family of receptor tyrosine kinases. We focus in particular on the complex multi-layered outer covering of the skin, the epidermis, which serves essential barrier and stress sensing/responding functions in terrestrial vertebrates. We will review emerging data showing that desmosome-IF connections, AJ-actin interactions, ErbB family members, and membrane tension are all polarized across the multiple layers of the regenerating epidermis. Importantly, their integration generates differentiation-specific roles in each layer of the epidermis that dictate the form and function of the tissue. In the basal layer, the onset of the differentiation-specific desmosomal cadherin desmoglein 1 (Dsg1) dials down EGFR signaling while working with classic cadherins to remodel cortical actin cytoskeleton and decrease membrane tension to promote cell delamination. In the upper layers, Dsg1 and E-cadherin cooperate to maintain high tension and tune EGFR and ErbB2 activity to create the essential tight junction barrier. Our final outlook discusses the emerging appreciation that the desmosome-IF scaffold not only creates the architecture required for skin’s physical barrier but also creates an immune barrier that keeps inflammation in check.
    Schlagwörter epidermal polarity ; desmoglein ; intermediate filament ; EGFR signaling ; actin cytoskeleton ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2022-05-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Polarity signaling balances epithelial contractility and mechanical resistance

    Matthias Rübsam / Robin Püllen / Frederik Tellkamp / Alessandra Bianco / Marc Peskoller / Wilhelm Bloch / Kathleen J. Green / Rudolf Merkel / Bernd Hoffmann / Sara A. Wickström / Carien M. Niessen

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Band 14

    Abstract: Abstract Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt ... ...

    Abstract Abstract Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known. Here we show that in stratifying epithelia the polarity protein aPKCλ controls the reorganization from stress fibers to cortical actomyosin during differentiation and upward movement of cells. Without aPKC, stress fibers are retained resulting in increased contractile prestress. This aberrant stress is counterbalanced by reorganization and bundling of keratins, thereby increasing mechanical resilience. Inhibiting contractility in aPKCλ−/− cells restores normal cortical keratin networks but also normalizes resilience. Consistently, increasing contractile stress is sufficient to induce keratin bundling and enhance resilience, mimicking aPKC loss. In conclusion, our data indicate that keratins sense the contractile stress state of stratified epithelia and balance increased contractility by mounting a protective response to maintain tissue integrity.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2023-05-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: E-cadherin binds to desmoglein to facilitate desmosome assembly

    Omer Shafraz / Matthias Rübsam / Sara N Stahley / Amber L Caldara / Andrew P Kowalczyk / Carien M Niessen / Sanjeevi Sivasankar

    eLife, Vol

    2018  Band 7

    Abstract: Desmosomes are adhesive junctions composed of two desmosomal cadherins: desmocollin (Dsc) and desmoglein (Dsg). Previous studies demonstrate that E-cadherin (Ecad), an adhesive protein that interacts in both trans (between opposing cells) and cis (on the ...

    Abstract Desmosomes are adhesive junctions composed of two desmosomal cadherins: desmocollin (Dsc) and desmoglein (Dsg). Previous studies demonstrate that E-cadherin (Ecad), an adhesive protein that interacts in both trans (between opposing cells) and cis (on the same cell surface) conformations, facilitates desmosome assembly via an unknown mechanism. Here we use structure-function analysis to resolve the mechanistic roles of Ecad in desmosome formation. Using AFM force measurements, we demonstrate that Ecad interacts with isoform 2 of Dsg via a conserved Leu-175 on the Ecad cis binding interface. Super-resolution imaging reveals that Ecad is enriched in nascent desmosomes, supporting a role for Ecad in early desmosome assembly. Finally, confocal imaging demonstrates that desmosome assembly is initiated at sites of Ecad mediated adhesion, and that Ecad-L175 is required for efficient Dsg2 and desmoplakin recruitment to intercellular contacts. We propose that Ecad trans interactions at nascent cell-cell contacts initiate the recruitment of Dsg through direct cis interactions with Ecad which facilitates desmosome assembly.
    Schlagwörter cell adhesion ; desmosomes ; cadherins ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 571
    Sprache Englisch
    Erscheinungsdatum 2018-07-01T00:00:00Z
    Verlag eLife Sciences Publications Ltd
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning

    Matthias Rübsam / Aaron F. Mertz / Akiharu Kubo / Susanna Marg / Christian Jüngst / Gladiola Goranci-Buzhala / Astrid C. Schauss / Valerie Horsley / Eric R. Dufresne / Markus Moser / Wolfgang Ziegler / Masayuki Amagai / Sara A. Wickström / Carien M. Niessen

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Band 16

    Abstract: In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in ... ...

    Abstract In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in lower layers while promoting TJ stability in the granular layer 2.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2017-11-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning

    Matthias Rübsam / Aaron F. Mertz / Akiharu Kubo / Susanna Marg / Christian Jüngst / Gladiola Goranci-Buzhala / Astrid C. Schauss / Valerie Horsley / Eric R. Dufresne / Markus Moser / Wolfgang Ziegler / Masayuki Amagai / Sara A. Wickström / Carien M. Niessen

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Band 16

    Abstract: In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in ... ...

    Abstract In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in lower layers while promoting TJ stability in the granular layer 2.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2017-11-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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