Keratins Regulate the Adhesive Properties of Desmosomal Cadherins through Signaling.
Keratins Regulate the Adhesive Properties of Desmosomal Cadherins through Signaling.
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角蛋白通过信号传导调节桥粒钙粘蛋白的粘附特性
DOI：
10.1016/j.jid.2017.08.033
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Spindler V
中科院分区：
文献类型：
--
作者：
Vielmuth F;Wanuske MT;Radeva MY;Hiermaier M;Kugelmann D;Walter E;Buechau F;Magin TM;Waschke J;Spindler V
严格控制的细胞间粘附对于表皮的完整性和功能至关重要。角蛋白丝细胞骨架锚定桥粒，桥粒是强细胞间粘附所需的超分子复合物。我们测试了角蛋白丝是否通过调节桥粒钙粘蛋白如桥粒芯蛋白（DSG）3的粘附特性来控制细胞粘附。光漂白实验后的原子力显微镜和荧光恢复表明，在缺乏所有角蛋白丝的小鼠角质形成细胞中，Dsg3粘附力和膜稳定性降低。受损的肌动蛋白细胞骨架也导致Dsg3固定减少，但不影响Dsg3的结合性能，表明后者是专门由角蛋白控制。减少结合力依赖于p38丝裂原活化蛋白激酶的活性，这是在角蛋白缺乏细胞失调。相反，抑制蛋白激酶C信号，这是已知的角蛋白控制，促进和空间稳定Dsg3介导的相互作用的膜。这些结果显示了一个以前未报道的机制，如何角蛋白稳定细胞间粘附的水平上的单个桥粒粘附分子。
Tightly controlled intercellular adhesion is crucial for the integrity and function of the epidermis. The keratin filament cytoskeleton anchors desmosomes, supramolecular complexes required for strong intercellular adhesion. We tested whether keratin filaments control cell adhesion by regulating the adhesive properties of desmosomal cadherins such as desmoglein (Dsg) 3. Atomic force microscopy and fluorescence recovery after photobleaching experiments showed reduced Dsg3 adhesive forces and membrane stability in murine keratinocytes lacking all keratin filaments. Impairment of the actin cytoskeleton also resulted in decreased Dsg3 immobilization but did not affect Dsg3 binding properties, indicating that the latter are exclusively controlled by keratins. Reduced binding forces were dependent on p38 mitogen-activated protein kinase activity, which was deregulated in keratin-deficient cells. In contrast, inhibition of protein kinase C signaling, which is known to be controlled by keratins, promoted and spatially stabilized Dsg3-mediated interactions in the membrane. These results show a previously unreported mechanism for how keratins stabilize intercellular adhesion on the level of single desmosomal adhesion molecules.
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影响因子：
6.5
作者：
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影响因子：
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作者：
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通讯作者：
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