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Yang, N, Williams, J, Pekovic-Vaughan, V, Wang, P, Olabi, S, McConnell, J, Gossan, N, Hughes, ATL, Cheung, J, Streuli, CH and Meng, Q-J (2017) Cellular mechano-environment regulates the mammary circadian clock. Nature Communications, 8. ISSN 2041-1723
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Yang et al (Meng) (2017) Cellular mechano-environment regulates the mammary circadian clock.pdf - Published Version Available under License Creative Commons Attribution. Download (6MB) | Preview |
Abstract
Circadian clocks drive B24 h rhythms in tissue physiology. They rely on transcriptional/ translational feedback loops driven by interacting networks of clock complexes. However, little is known about how cell-intrinsic circadian clocks sense and respond to their microenvironment. Here, we reveal that the breast epithelial clock is regulated by the mechano-chemical stiffness of the cellular microenvironment in primary cell culture. Moreover, the mammary clock is controlled by the periductal extracellular matrix in vivo, which contributes to a dampened circadian rhythm during ageing. Mechanistically, the tension sensing cell-matrix adhesion molecule, vinculin, and the Rho/ROCK pathway, which transduces signals provided by extracellular stiffness into cells, regulate the activity of the core circadian clock complex. We also show that genetic perturbation, or age-associated disruption of self-sustained clocks, compromises the self-renewal capacity of mammary epithelia. Thus, circadian clocks are mechano-sensitive, providing a potential mechanism to explain how ageing influences their amplitude and function.
| Item Type: | Article |
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| Uncontrolled Keywords: | MD Multidisciplinary |
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology |
| Divisions: | Natural Sciences & Psychology (closed 31 Aug 19) |
| Publisher: | Nature Publishing Group |
| Related URLs: | |
| Date Deposited: | 05 Apr 2018 10:12 |
| Last Modified: | 04 Sep 2021 10:36 |
| DOI or ID number: | 10.1038/ncomms14287 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/8416 |
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