Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα
Keratin Isotypes Control Desmosome Stability and Dynamics through PKCα
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DOI：
10.1038/jid.2015.403
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发表时间：
2016-01-01
影响因子：
6.5
通讯作者：
Magin, Thomas M.
中科院分区：
文献类型：
--
作者：
Loschke, Fanny;Homberg, Melanie;Magin, Thomas M.
桥粒组分和角蛋白的表达和相互作用提供稳定的细胞凝聚力并保护表皮免受各种类型的应力。角蛋白细胞骨架和桥粒的分化特异性同种型组成被认为是粘附强度的主要决定因素。作为支持，伤口愈合的特征在于桥粒粘附的短暂减少，伴随着角蛋白K6/K16/K17的表达增加，以K1/K10为代价。改变角蛋白表达对桥粒组成和粘附的意义在机制和功能水平上仍不完全清楚。在这里，我们研究了K5/K14或K6/K17对桥粒粘附的各自贡献，其在缺乏所有角蛋白的角质形成细胞中的稳定再表达。这表明，K5/K14细丝支持稳定的桥粒，而“伤口愈合”角蛋白K6/K17诱导升高的蛋白激酶C α-血红蛋白介导的桥粒解体和随后的上皮片的不稳定。此外，我们的数据表明，K5/K14螯合蛋白激酶C α在细胞质中，而K6/K17或所有角蛋白的缺乏使蛋白激酶C α易位到质膜和诱导桥粒解体。功能获得和丧失实验支持K5通过蛋白激酶C α在桥粒稳定性控制中的主要作用。我们的数据表明，角蛋白同种型不同，并通过调节细胞间粘附特异性地调节伤口愈合和侵袭。
Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The differentiation-specific isotype composition of the keratin cytoskeleton and desmosomes is regarded as a major determinant of adhesive strength. In support, wound healing is characterized by a transient decrease in desmosomal adhesion accompanied by increased expression of keratins K6/K16/K17 at the expense of K1/K10. The significance of altered keratin expression for desmosomal composition and adhesion remains incompletely understood at a mechanistic and functional level. Here, we investigated the respective contribution of K5/K14 or K6/K17 to desmosome adhesion, on their stable re-expression in keratinocytes lacking all keratins. This revealed that K5/K14 filaments support stable desmosomes, whereas "wound healing" keratins K6/K17 induce elevated protein kinase C alphaemediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester protein kinase C alpha in the cytoplasm, whereas K6/K17 or the absence of all keratins enables protein kinase C alpha translocation to the plasma membrane and induction of desmosome disassembly. Gain- and loss-of-function experiments support a major role of K5 in desmosome stability control via protein kinase C alpha. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion.