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0This research identifies microtubule architecture as a central regulator of cellular mechanotransduction, specifically influencing the YAP/TAZ signaling pathway. The study demonstrates that mechanical forces cause microtubules to reorganize from a cage-like structure into a radial array centered at the nucleus. This shift facilitates the degradation of AMOT, a protein that acts as a mechanical rheostat by sequestering YAP/TAZ in the cytoplasm when cells are in a "mechano-OFF" state. By utilizing the centrosomal proteasome, the cell effectively removes these inhibitors to allow for nuclear entry of YAP/TAZ and subsequent gene expression. The authors further establish a mechanical continuum involving F-actin stress fibers and the nuclear envelope that coordinates this cytoskeletal restructuring. Ultimately, the research highlights how Hippo signaling and oncogenic pathways can disrupt this checkpoint to drive tumor growth.
References:
Vanni G, Citron A, Suli A, et al. Microtubule architecture connects AMOT stability to YAP/TAZ mechanotransduction and Hippo signalling[J]. Nature Cell Biology, 2025, 27(10): 1725-1738.
