Abstract
AbstractEpithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known. Here we show that in stratifying epithelia the polarity protein aPKCλ controls the reorganization from stress fibers to cortical actomyosin during differentiation and upward movement of cells. Without aPKC, stress fibers are retained resulting in increased contractile prestress. This aberrant stress is counterbalanced by reorganization and bundling of keratins, thereby increasing mechanical resilience. Inhibiting contractility in aPKCλ−/− cells restores normal cortical keratin networks but also normalizes resilience. Consistently, increasing contractile stress is sufficient to induce keratin bundling and enhance resilience, mimicking aPKC loss. In conclusion, our data indicate that keratins sense the contractile stress state of stratified epithelia and balance increased contractility by mounting a protective response to maintain tissue integrity.
Funder
Universitätsklinikum Köln
Publisher
Springer Science and Business Media LLC
Reference54 articles.
1. Kubo, A., Nagao, K. & Amagai, M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J. Clin. Invest. 122(2), 440–447 (2012).
2. Biggs, L. C., Kim, C. S., Miroshnikova, Y. A. & Wickström, S. A. Mechanical forces in the skin: Roles in tissue architecture, stability, and function. J. Invest. Dermatol. 140, 284–290 (2020).
3. Moreci, R. S. & Lechler, T. Epidermal structure and differentiation. Curr. Biol. 30, R144–R149 (2020).
4. Rübsam, M. et al. Adherens junctions and desmosomes coordinate mechanics and signaling to orchestrate tissue morphogenesis and function: An evolutionary perspective. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a029207 (2018).
5. Sumigray, K. D. & Lechler, T. Cell Adhesion in Epidermal Development and Barrier Formation. Current Topics in Developmental Biology Vol. 112 (Elsevier Inc, 2015).
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献