The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function
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 pro...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.903696/full |
| _version_ | 1828809659318796288 |
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| author | Kathleen J. Green Kathleen J. Green Kathleen J. Green Carien M. Niessen Carien M. Niessen Carien M. Niessen Matthias Rübsam Matthias Rübsam Matthias Rübsam Bethany E. Perez White Bethany E. Perez White Joshua A. Broussard Joshua A. Broussard Joshua A. Broussard |
| author_facet | Kathleen J. Green Kathleen J. Green Kathleen J. Green Carien M. Niessen Carien M. Niessen Carien M. Niessen Matthias Rübsam Matthias Rübsam Matthias Rübsam Bethany E. Perez White Bethany E. Perez White Joshua A. Broussard Joshua A. Broussard Joshua A. Broussard |
| author_sort | Kathleen J. Green |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T08:59:20Z |
| format | Article |
| id | doaj.art-a59d62f411c24d0ba8533fc798c3c3c3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T08:59:20Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a59d62f411c24d0ba8533fc798c3c3c32022-12-22T00:29:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.903696903696The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and FunctionKathleen J. Green0Kathleen J. Green1Kathleen J. Green2Carien M. Niessen3Carien M. Niessen4Carien M. Niessen5Matthias Rübsam6Matthias Rübsam7Matthias Rübsam8Bethany E. Perez White9Bethany E. Perez White10Joshua A. Broussard11Joshua A. Broussard12Joshua A. Broussard13Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United StatesDepartment Cell Biology of the Skin, University Hospital of Cologne, University of Cologne, Cologne, GermanyCologne Excellence Cluster on Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine (CMMC), University Hospital of Cologne, University of Cologne, Cologne, GermanyDepartment Cell Biology of the Skin, University Hospital of Cologne, University of Cologne, Cologne, GermanyCologne Excellence Cluster on Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, University of Cologne, Cologne, GermanyCenter for Molecular Medicine (CMMC), University Hospital of Cologne, University of Cologne, Cologne, GermanyDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United StatesDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United StatesRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United StatesWhile 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.https://www.frontiersin.org/articles/10.3389/fcell.2022.903696/fullepidermal polaritydesmogleinintermediate filamentEGFR signalingactin cytoskeleton |
| spellingShingle | Kathleen J. Green Kathleen J. Green Kathleen J. Green Carien M. Niessen Carien M. Niessen Carien M. Niessen Matthias Rübsam Matthias Rübsam Matthias Rübsam Bethany E. Perez White Bethany E. Perez White Joshua A. Broussard Joshua A. Broussard Joshua A. Broussard The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function Frontiers in Cell and Developmental Biology epidermal polarity desmoglein intermediate filament EGFR signaling actin cytoskeleton |
| title | The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function |
| title_full | The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function |
| title_fullStr | The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function |
| title_full_unstemmed | The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function |
| title_short | The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function |
| title_sort | desmosome keratin scaffold integrates erbb family and mechanical signaling to polarize epidermal structure and function |
| topic | epidermal polarity desmoglein intermediate filament EGFR signaling actin cytoskeleton |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.903696/full |
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