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Access through your institution Buy or subscribe The receptor tyrosine kinase DDR1 is mechanoresponsive to extracellular matrix (ECM) stiffness and affects Hippo and YAP signalling, but the
precise mechanisms of this are unclear. Liu et al. report that DDR1 regulates YAP and that ECM stiffness can stimulate liquid–liquid phase separation of both DDR1 and the Hippo pathway
kinase LATS1. The authors found that vascular smooth muscle cells grown on stiffer substrata, as well as nephrectomy-induced (Nx) arterial stiffening in mice, transcriptionally upregulated
genes encoding components of the Hippo pathway. DDR1 forms liquid-like droplets in vitro, and formed similar puncta in their Nx mouse model in vivo. In response to stiffness, DDR1
co-condenses with LATS1 to inactivate LATS1. In an ex vivo arterial stiffening assay, inhibition of DDR1 diminished phosphorous-induced stiffening in a LATS1-dependent manner. Finally, DDR1
depletion in their Nx mouse model decreased arterial stiffening, calcium deposition, and collagen deposition on vessel walls in a LATS1-dependent manner. This is a preview of subscription
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* Learn about institutional subscriptions * Read our FAQs * Contact customer support AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Cell Biology https://www.nature.com/ncb Daryl J. V.
David Authors * Daryl J. V. David View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Daryl J. V. David. RIGHTS AND
PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE David, D.J.V. Liquid DDR1 responding to stiffness. _Nat Cell Biol_ 25, 6 (2023).
https://doi.org/10.1038/s41556-022-01078-5 Download citation * Published: 17 January 2023 * Issue Date: January 2023 * DOI: https://doi.org/10.1038/s41556-022-01078-5 SHARE THIS ARTICLE
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