例如:"lncRNA", "apoptosis", "WRKY"

Zyxin regulates endothelial von Willebrand factor secretion by reorganizing actin filaments around exocytic granules.

Nat Commun. 2017 Mar 03;8:14639
Xiaofan Han 1 , Pin Li 1 , Zhenghao Yang 1 , Xiaoshuai Huang 2 , Guoqin Wei 1 , Yujie Sun 3 , Xuya Kang 1 , Xueting Hu 1 , Qiuping Deng 1 , Liangyi Chen 2 , Aibin He 2 , Yingqing Huo 1 , Dong Li 4 , Eric Betzig 5 , Jincai Luo 1
Xiaofan Han 1 , Pin Li 1 , Zhenghao Yang 1 , Xiaoshuai Huang 2 , Guoqin Wei 1 , Yujie Sun 3 , Xuya Kang 1 , Xueting Hu 1 , Qiuping Deng 1 , Liangyi Chen 2 , Aibin He 2 , Yingqing Huo 1 , Dong Li 4 , Eric Betzig 5 , Jincai Luo 1
+ et al

[No authors listed]

Author information
  • 1 Laboratory of Vascular Biology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
  • 2 The State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Laboratory of Institute of Molecular Medicine, Peking University, Beijing 100871, China.
  • 3 State Key Laboratory of Biomembrane and Membrane Biotechnology, Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
  • 4 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.

摘要


Endothelial exocytosis of Weibel-Palade body (WPB) is one of the first lines of defence against vascular injury. However, the mechanisms that control WPB exocytosis in the final stages (including the docking, priming and fusion of granules) are poorly understood. Here we show that the focal adhesion protein zyxin is crucial in this process. Zyxin downregulation inhibits the secretion of von Willebrand factor (VWF), the most abundant cargo in WPBs, from human primary endothelial cells (ECs) induced by cAMP agonists. Zyxin-deficient mice exhibit impaired epinephrine-stimulated VWF release, prolonged bleeding time and thrombosis, largely due to defective endothelial secretion of VWF. Using live-cell super-resolution microscopy, we visualize previously unappreciated reorganization of pre-existing actin filaments around WPBs before fusion, dependent on zyxin and an interaction with the actin crosslinker α-actinin. Our findings identify zyxin as a physiological regulator of endothelial exocytosis through reorganizing local actin network in the final stage of exocytosis.