Cellular mechano-environment regulates the mammary circadian clock

Yang, Nan, Williams, Jack, Pekovic-Vaughan, Vanja ORCID: 0000-0002-7876-652X, Wang, Pengbo, Olabi, Safiah, McConnell, James, Gossan, Nicole, Hughes, Alun, Cheung, Julia, Streuli, Charles H
et al (show 1 more authors) (2017) Cellular mechano-environment regulates the mammary circadian clock. Nature Communications, 8.

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Circadian clocks drive ∼24 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
Depositing User: Symplectic Admin
Date Deposited: 30 Aug 2017 15:04
Last Modified: 07 Jun 2021 20:11
DOI: 10.1038/ncomms14287
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3009243