التفاصيل البيبلوغرافية
| العنوان: |
Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation. |
| المؤلفون: |
Keiko Nonomura, Lukacs, Viktor, Sweet, Daniel T., Goddard, Lauren M., Akemi Kanie, Whitwam, Tess, Ranade, Sanjeev S., Toshihiko Fujimori, Kahn, Mark L., Patapoutian, Ardem |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 12/11/2018, Vol. 115 Issue 50, p12817-12822, 6p |
| مصطلحات موضوعية: |
LYMPHATICS, MECHANOTRANSDUCTION (Cytology), ION channels, ENDOTHELIAL cells, PLEURAL effusions, BLOOD vessels |
| مستخلص: |
PIEZO1 is a cation channel that is activated by mechanical forces such as fluid shear stress or membrane stretch. PIEZO1 loss-of-function mutations in patients are associated with congenital lymphedema with pleural effusion. However, the mechanistic link between PIEZO1 function and the development or function of the lymphatic system is currently unknown. Here, we analyzed two mouse lines lacking PIEZO1 in endothelial cells (via Tie2Cre or Lyve1Cre) and found that they exhibited pleural effusion and died postnatally. Strikingly, the number of lymphatic valves was dramatically reduced in these mice. Lymphatic valves are essential for ensuring proper circulation of lymph. Mechanical forces have been implicated in the development of lymphatic vasculature and valve formation, but the identity of mechanosensors involved is unknown. Expression of FOXC2 and NFATc1, transcription factors known to be required for lymphatic valve development, appeared normal in Tie2Cre;Piezo1cKO mice. However, the process of protrusion in the valve leaflets, which is associated with collective cell migration, actin polymerization, and remodeling of cell-cell junctions, was impaired in Tie2Cre;Piezo1cKO mice. Consistent with these genetic findings, activation of PIEZO1 by Yoda1 in cultured lymphatic endothelial cells induced active remodeling of actomyosin and VE-cadherin+ cell-cell adhesion sites. Our analysis provides evidence that mechanically activated ion channel PIEZO1 is a key regulator of lymphatic valve formation. [ABSTRACT FROM AUTHOR] |
|
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
