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Keiichiro Tanaka
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Journal Articles
Abhishek Kumar, Maria S. Shutova, Keiichiro Tanaka, Daniel V. Iwamoto, David A. Calderwood, Tatyana M. Svitkina, Martin A. Schwartz
Journal:
Journal of Cell Biology
Journal of Cell Biology (2019) 218 (8): 2481–2491.
Published: 17 July 2019
Abstract
Cell sensing of externally applied mechanical strain through integrin-mediated adhesions is critical in development and physiology of muscle, lung, tendon, and arteries, among others. We examined the effects of strain on force transmission through the essential cytoskeletal linker talin. Using a fluorescence-based talin tension sensor (TS), we found that uniaxial stretch of cells on elastic substrates increased tension on talin, which was unexpectedly independent of the orientation of the focal adhesions relative to the direction of strain. High-resolution electron microscopy of the actin cytoskeleton revealed that stress fibers (SFs) are integrated into an isotropic network of cortical actin filaments in which filamin A (FlnA) localizes preferentially to points of intersection between SFs and cortical actin. Knockdown (KD) of FlnA resulted in more isolated, less integrated SFs. After FlnA KD, tension on talin was polarized in the direction of stretch, while FlnA reexpression restored tensional symmetry. These data demonstrate that a FlnA-dependent cortical actin network distributes applied forces over the entire cytoskeleton–matrix interface.
Includes: Supplementary data
Journal Articles
Abhishek Kumar, Mingxing Ouyang, Koen Van den Dries, Ewan James McGhee, Keiichiro Tanaka, Marie D. Anderson, Alexander Groisman, Benjamin T. Goult, Kurt I. Anderson, Martin A. Schwartz
Journal:
Journal of Cell Biology
Journal of Cell Biology (2016) 214 (2): 231.
Published: 18 July 2016
Journal Articles
Abhishek Kumar, Mingxing Ouyang, Koen Van den Dries, Ewan James McGhee, Keiichiro Tanaka, Marie D. Anderson, Alexander Groisman, Benjamin T. Goult, Kurt I. Anderson, Martin A. Schwartz
Journal:
Journal of Cell Biology
Journal of Cell Biology (2016) 213 (3): 371–383.
Published: 09 May 2016
Abstract
Integrin-dependent adhesions are mechanosensitive structures in which talin mediates a linkage to actin filaments either directly or indirectly by recruiting vinculin. Here, we report the development and validation of a talin tension sensor. We find that talin in focal adhesions is under tension, which is higher in peripheral than central adhesions. Tension on talin is increased by vinculin and depends mainly on actin-binding site 2 (ABS2) within the middle of the rod domain, rather than ABS3 at the far C terminus. Unlike vinculin, talin is under lower tension on soft substrates. The difference between central and peripheral adhesions requires ABS3 but not vinculin or ABS2. However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3. These results indicate that central versus peripheral adhesions must be organized and regulated differently, and that ABS2 and ABS3 have distinct functions in spatial variations and stiffness sensing. Overall, these results shed new light on talin function and constrain models for cellular mechanosensing.
Includes: Supplementary data