角蛋白
细胞生物学
中间灯丝
蛋白激酶B
背景(考古学)
化学
桥粒胶蛋白3
角蛋白14
生物
细胞骨架
信号转导
细胞
免疫学
生物化学
抗体
古生物学
转基因小鼠
基因
自身免疫性疾病
转基因
作者
Stefan Kippenberger,Johannes Kleemann,Markus Meissner,Katja Steinhorst,Jutta Müller,Christos C. Zouboulis,Roland Kaufmann,Nadja Zöller
标识
DOI:10.1016/j.jdermsci.2017.11.011
摘要
Mechanical stress is an ubiquitous challenge of human cells with fundamental impact on cell physiology. Previous studies have shown that stretching promotes signalling cascades involved in proliferation and tissue enlargement.The present study is dedicated to learn more about cellular structures contributing to perception and signal transmission of cell stretch. In particular, we hypothesized that desmosmal contacts and the adjacent keratin filament build an intercellular matrix providing information about the mechanical load.Epidermal cells with different keratin equipment were seeded on flexible silicon dishes and stretched. As read out parameter the activation of PKB/Akt and p44/42 was monitored by Western blotting. Likewise desomosomal contacts were manipulated by depletion or addition of calcium. Moreover, desmoglein 3 and desmocollin 3 were blocked by either specific antibodies or siRNA.It was found that the omission of calcium from the medium, a necessary cofactor for desmosomal cadherins, inhibited stretch mediated activation of PKB/Akt and p44/42. The relevance of desmosomes in this context was further substantiated by experiments using a desmoglein 3 blocking antibody (AK23) and siRNA against desmocollin 3. Moreover, disruption of the keratin filament by sodium orthovanadate also abrogates PKB/Akt and p44/42 activation in response to stretch. Likewise, KEB-7 keratinocytes harbouring a mutation in the keratin 14 gene and genetically modified keratinocytes devoid of any keratin show an altered signalling after stretch indicating the relevance of the keratin filament in this context.Besides their important role in cell architecture our results identify desmosomes and keratins as mechanosensing structures.
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