期刊
JOURNAL OF CELL BIOLOGY
卷 219, 期 2, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201904137
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资金
- Netherlands Organization for Scientific Research as part of the National Roadmap Largescale Research Facilities of the Netherlands Proteins@Work [184.032.201]
- China Scholarship Council
- AXA Research Fund postdoctoral grant [16-AXA-PDOC-004]
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 alpha 6 beta 4 exhibit increased focal adhesion formation, cell spreading, and traction-force generation. Moreover, disruption of the interaction between alpha 6 beta 4 and intermediate filaments or laminin-332 results in similar phenotypical changes. We further demonstrate that integrin alpha 6 beta 4 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 alpha V beta 5 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.
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