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Keratin Filaments Regulate Binding Properties of the Desmosomal Adhesion Molecule Desmoglein 3
Author(s) -
Vielmuth Franziska,
Loschke Fanny,
Magin Thomas M.,
Waschke Jens,
Spindler Volker
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.305.4
Subject(s) - desmosome , desmoglein 3 , keratin , desmoglein , intermediate filament , microbiology and biotechnology , chemistry , cadherin , cell junction , desmoplakin , cell adhesion , cell adhesion molecule , adhesion , cytoskeleton , biophysics , biology , cell , immunology , biochemistry , paleontology , autoimmune disease , organic chemistry , antibody
Desmosomes are supramolecular protein complexes required for strong intercellular adhesion. Accordingly, they are most abundant in tissues exposed to pronounced mechanical stress, such as the epidermis. In desmosomes, the interaction with adjacent cells is provided by desmosomal cadherins which are intracellularly linked with the intermediate filament cytoskeleton by several adapter proteins. Using atomic force microscopy (AFM) on living keratinocytes, we recently showed that binding forces of the desmosomal cadherin desmoglein 3 (Dsg3) are not uniformly distributed but are higher at cell borders compared to cell surface areas. In view of the compromised adhesion resulting from intermediate filament loss, we here tested the relevance of keratins, the intermediate filament proteins of epithelial cells, for the binding properties of Dsg3. In cultured human keratinocytes, Dsg3, the adapter molecule desmoplakin and keratin filaments, assembles on the cell surface away from junctions. Murine keratinocytes lacking all keratin filaments (KtyII ko) displayed reduced intercellular adhesion compared to controls (KtyII wt). Surprisingly, the protein levels and membrane localization of Dsg3 was increased in KtyII cells. In line with this, by using AFM, a higher frequency of Dsg3‐mediated binding events was observed in Ktyll ko cells. However, the binding forces of individual Dsg3‐mediated binding events were significantly reduced compared to KtyII wt cells. Our data for the first time show that keratins, potentially by anchorage to the desmosomal complex, regulate binding properties of desmosomal cadherins and therefore provide new insights into the mechanisms of desmosomal adhesion.