当前位置: X-MOL 学术The Journal of Cell Biology › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hemidesmosomes modulate force generation via focal adhesions
The Journal of Cell Biology Pub Date : 2020-01-08 , DOI: 10.1083/jcb.201904137
Wei Wang 1 , Alba Zuidema 1 , Lisa Te Molder 1 , Leila Nahidiazar 1 , Liesbeth Hoekman 2 , Thomas Schmidt 3 , Stefano Coppola 3 , Arnoud Sonnenberg 1
Affiliation  

Hemidesmosomes are specialized cell-matrix adhesion structures that are associated with the keratin cytoskeleton. Although the adhesion function of hemidesmosomes has been extensively studied, their role in mechanosignaling and transduction remains largely unexplored. Here, we show that keratinocytes lacking hemidesmosomal integrin α6β4 exhibit increased focal adhesion formation, cell spreading, and traction-force generation. Moreover, disruption of the interaction between α6β4 and intermediate filaments or laminin-332 results in similar phenotypical changes. We further demonstrate that integrin α6β4 regulates the activity of the mechanosensitive transcriptional regulator YAP through inhibition of Rho–ROCK–MLC– and FAK–PI3K–dependent signaling pathways. Additionally, increased tension caused by impaired hemidesmosome assembly leads to a redistribution of integrin αVβ5 from clathrin lattices to focal adhesions. Our results reveal a novel role for hemidesmosomes as regulators of cellular mechanical forces and establish the existence of a mechanical coupling between adhesion complexes.

中文翻译:

半桥粒通过粘着斑调节力的产生

半桥粒是与角蛋白细胞骨架相关的特殊细胞基质粘附结构。尽管半桥粒的粘附功能已被广泛研究,但它们在机械信号传导和转导中的作用仍然很大程度上未被探索。在这里,我们发现缺乏半桥粒整合素α6β4的角质形成细胞表现出增加的粘着斑形成、细胞扩散和牵引力产生。此外,破坏 α6β4 和中间丝或层粘连蛋白 332 之间的相互作用会导致类似的表型变化。我们进一步证明整合素 α6β4 通过抑制 Rho-ROCK-MLC- 和 FAK-PI3K 依赖性信号通路来调节机械敏感转录调节因子 YAP 的活性。此外,半桥粒组装受损导致张力增加,导致整合素 αVβ5 从网格蛋白晶格重新分布到粘着斑。我们的结果揭示了半桥粒作为细胞机械力调节器的新作用,并确定了粘附复合物之间机械耦合的存在。
更新日期:2020-01-08
down
wechat
bug