期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 40, 页码 10648-10653出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1701136114
关键词
cell migration; mechanosensing; fluorescence polarization microscopy
资金
- MBL/University of Chicago
- NIH [5R13GM085967, CA31798, GM100160, GM092802, GM114274]
- Howard Hughes Medical Institute Summer Institute at MBL
- Human Frontier Science Program (HFSP) [LT000096/2011-C]
- HFSP [RGP0027/2012]
- Wellcome Trust
- National Heart, Lung, and Blood Institute Division of Intramural Research
Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization-or contractility-driven retrograde flow of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-alpha V beta 3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据