Sumigray Kaelyn, Zhou Kang, Lechler Terry
Depts. of Dermatology and Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
PLoS One. 2014 Jul 9;9(7):e101824. doi: 10.1371/journal.pone.0101824. eCollection 2014.
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.
桥粒在多种疾病状态下会受到干扰，包括遗传疾病、自身免疫性疾病和细菌性疾病。在此，我们报告了桥粒功能丧失后其他细胞间粘附结构的意外变化。我们发现，通过缺失核心桥粒蛋白桥粒斑蛋白或用致病性抗桥粒芯糖蛋白3（Dsg3）抗体处理来干扰桥粒，会导致黏着连接发生变化，这与张力增加一致。在桥粒斑蛋白缺失的表皮中，肌球蛋白IIA的总量增加，并且在桥粒斑蛋白缺失的和抗Dsg3处理的小鼠角质形成细胞中，肌球蛋白IIA高度定位于细胞接触部位。抑制肌球蛋白II的活性可逆转桥粒破坏后黏着连接的变化。皮质肌球蛋白IIA的增加促进了上皮片层的脆弱性，因为肌球蛋白IIA缺失的细胞更不易受到抗Dsg3抗体的破坏。除了黏着连接的变化外，我们还发现许多紧密连接蛋白基因的表达显著增加，这些基因编码提供屏障功能的紧密连接的跨膜成分。这些数据表明，桥粒破坏会导致广泛的转录和翻译后变化，从而改变其他细胞粘附结构的活性。
