PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus
Abstract Critical for the maintenance of epidermal integrity and function are attachments between intermediate filaments (IF) and intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential for anchoring IF to the junction. DP-IF interactions ar...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-37874-8 |
| _version_ | 1797452717159874560 |
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| author | Abbey L. Perl Jennifer L. Koetsier Kathleen J. Green |
| author_facet | Abbey L. Perl Jennifer L. Koetsier Kathleen J. Green |
| author_sort | Abbey L. Perl |
| collection | DOAJ |
| description | Abstract Critical for the maintenance of epidermal integrity and function are attachments between intermediate filaments (IF) and intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential for anchoring IF to the junction. DP-IF interactions are regulated by a phospho-regulatory motif within the DP C-terminus controlling keratinocyte intercellular adhesion. Here we identify the protein phosphatase 2A (PP2A)-B55α holoenzyme as the major serine/threonine phosphatase regulating DP’s C-terminus and consequent intercellular adhesion. Using a combination of chemical and genetic approaches, we show that the PP2A-B55α holoenzyme interacts with DP at intercellular membranes in 2D- and 3D- epidermal models and human skin samples. Our experiments demonstrate that PP2A-B55α regulates the phosphorylation status of junctional DP and is required for maintaining strong desmosome-mediated intercellular adhesion. These data identify PP2A-B55α as part of a regulatory module capable of tuning intercellular adhesion strength and a candidate disease target in desmosome-related disorders of the skin and heart. |
| first_indexed | 2024-03-09T15:12:41Z |
| format | Article |
| id | doaj.art-57f9a37880ff4dfe8d2f72239da73708 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:12:41Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-57f9a37880ff4dfe8d2f72239da737082023-11-26T13:16:04ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-37874-8PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminusAbbey L. Perl0Jennifer L. Koetsier1Kathleen J. Green2Department of Pathology, Feinberg School of Medicine, Northwestern UniversityDepartment of Pathology, Feinberg School of Medicine, Northwestern UniversityDepartment of Pathology, Feinberg School of Medicine, Northwestern UniversityAbstract Critical for the maintenance of epidermal integrity and function are attachments between intermediate filaments (IF) and intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential for anchoring IF to the junction. DP-IF interactions are regulated by a phospho-regulatory motif within the DP C-terminus controlling keratinocyte intercellular adhesion. Here we identify the protein phosphatase 2A (PP2A)-B55α holoenzyme as the major serine/threonine phosphatase regulating DP’s C-terminus and consequent intercellular adhesion. Using a combination of chemical and genetic approaches, we show that the PP2A-B55α holoenzyme interacts with DP at intercellular membranes in 2D- and 3D- epidermal models and human skin samples. Our experiments demonstrate that PP2A-B55α regulates the phosphorylation status of junctional DP and is required for maintaining strong desmosome-mediated intercellular adhesion. These data identify PP2A-B55α as part of a regulatory module capable of tuning intercellular adhesion strength and a candidate disease target in desmosome-related disorders of the skin and heart.https://doi.org/10.1038/s41598-023-37874-8 |
| spellingShingle | Abbey L. Perl Jennifer L. Koetsier Kathleen J. Green PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus Scientific Reports |
| title | PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus |
| title_full | PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus |
| title_fullStr | PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus |
| title_full_unstemmed | PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus |
| title_short | PP2A-B55alpha controls keratinocyte adhesion through dephosphorylation of the Desmoplakin C-terminus |
| title_sort | pp2a b55alpha controls keratinocyte adhesion through dephosphorylation of the desmoplakin c terminus |
| url | https://doi.org/10.1038/s41598-023-37874-8 |
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