2026-04-22 ロックフェラー大学
＜関連情報＞
- https://www.rockefeller.edu/news/39413-cells-mechanical-forces-cancer-disease/
- https://www.nature.com/articles/s41586-026-10398-7
- https://www.science.org/doi/10.1126/sciadv.abl4733
ミオシンの力は、機械感受性タンパク質の認識のためにFアクチンを再構築する Myosin forces remodel F-actin for mechanosensitive protein recognition
Ayala G. Carl,Matthew J. Reynolds,Xiaoyu Sun,Pinar S. Gurel,Donovan Y. Z. Phua,Keith Hamilton,Lin Mei,John W. Watters,Yasuharu Takagi,Alex J. Noble,James R. Sellers & Gregory M. Alushin
Nature Published:22 April 2026
DOI:https://doi.org/10.1038/s41586-026-10398-7
Abstract
Cells interface mechanically with their surroundings through cytoskeleton-linked adhesions1,2, which enable them to sense physical cues that instruct development and drive diseases such as cancer3,4,5. Contractile forces generated by myosin motor proteins6,7 mediate these mechanical signal transduction processes through unknown protein structural mechanisms. Here we show that force generated by myosin elicits structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin8. Using correlative cryo-fluorescence microscopy and cryo-electron tomography, we identify F-actin featuring sinusoidal regions of nanoscale oscillating curvature at cytoskeleton–adhesion interfaces enriched in zyxin, a marker of actin–myosin-generated traction forces9. We introduce a reconstitution system for visualizing F-actin in the presence of myosin forces using cryo-electron microscopy, which reveals morphologically similar F-actin supercoils. In simulations, compressive forces that mimic myosin activity produce supercoils, which can be generated by ensembles of asynchronous motors regardless of their directionality. Three-dimensional reconstruction of supercoils uncovers extensive asymmetric remodelling of the helical lattice of F-actin. This is recognized by α-catenin, which binds cooperatively along individual strands, preferentially engaging interfaces that feature extended inter-subunit distances while simultaneously suppressing rotational deviations to regularize the lattice. In sum, we find that myosin forces can deform F-actin, generating a conformational landscape that is detected and reciprocally modulated by a mechanosensitive protein, providing a direct structural glimpse at active force transduction through the cytoskeleton.
機械受容性ステレオシリアにおけるミオシン15によるアクチンダイナミクスの調節可能な制御の構造的基盤 Structural basis for tunable control of actin dynamics by myosin-15 in mechanosensory stereocilia
Rui Gong, Fangfang Jiang, Zane G. Moreland, Matthew J. Reynolds, […] , and Gregory M. Alushin
Science Advances Published:20 Jul 2022
DOI:https://doi.org/10.1126/sciadv.abl4733
Abstract
The motor protein myosin-15 is necessary for the development and maintenance of mechanosensory stereocilia, and mutations in myosin-15 cause hereditary deafness. In addition to transporting actin regulatory machinery to stereocilia tips, myosin-15 directly nucleates actin filament (“F-actin”) assembly, which is disrupted by a progressive hearing loss mutation (p.D1647G, “jordan”). Here, we present cryo–electron microscopy structures of myosin-15 bound to F-actin, providing a framework for interpreting the impacts of deafness mutations on motor activity and actin nucleation. Rigor myosin-15 evokes conformational changes in F-actin yet maintains flexibility in actin’s D-loop, which mediates inter-subunit contacts, while the jordan mutant locks the D-loop in a single conformation. Adenosine diphosphate–bound myosin-15 also locks the D-loop, which correspondingly blunts actin-polymerization stimulation. We propose myosin-15 enhances polymerization by bridging actin protomers, regulating nucleation efficiency by modulating actin’s structural plasticity in a myosin nucleotide state–dependent manner. This tunable regulation of actin polymerization could be harnessed to precisely control stereocilium height.
