title: Cell-cell adhesions and cell contractility are upregulated upon desmosome disruption.
abstract: Desmosomes are perturbed in a number of disease states - including genetic disorders, autoimmune and bacterial diseases. Here, we report unexpected changes in other cell-cell adhesion structures upon loss of desmosome function. We found that perturbation of desmosomes by either loss of the core desmosomal protein desmoplakin or treatment with pathogenic anti-desmoglein 3 (Dsg3) antibodies resulted in changes in adherens junctions consistent with increased tension. The total amount of myosin IIA was increased in desmoplakin-null epidermis, and myosin IIA became highly localized to cell contacts in both desmoplakin-null and anti-Dsg3-treated mouse keratinocytes. Inhibition of myosin II activity reversed the changes to adherens junctions seen upon desmosome disruption. The increased cortical myosin IIA promoted epithelial sheet fragility, as myosin IIA-null cells were less susceptible to disruption by anti-Dsg3 antibodies. In addition to the changes in adherens junctions, we found a significant increase in the expression of a number of claudin genes, which encode for transmembrane components of the tight junction that provide barrier function. These data demonstrate that desmosome disruption results in extensive transcriptional and posttranslational changes that alter the activity of other cell adhesion structures.
authors.affiliation: Depts. of Dermatology and Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Kaelyn
authors.initials: K
authors.lastname: Sumigray
authors.affiliation: Depts. of Dermatology and Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Depts. of Dermatology and Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Terry
authors.initials: T
authors.lastname: Lechler
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D057167:Claudins / Q000378:metabolism; D051184:Desmoglein 3 / Q000037:antagonists & inhibitors; D051180:Desmoplakins / Q000235:genetics* / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004622:Embryo, Mammalian / Q000166:cytology*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism
chemical_list: D000906:Antibodies; D057167:Claudins; D051184:Desmoglein 3; D051180:Desmoplakins; C495300:Dsg3 protein, mouse; D024507:Nonmuscle Myosin Type IIA