Imperial College London
Alternate

DrArmandoDel Rio Hernandez

Faculty of Engineering, Department of Bioengineering

Reader in Cellular and Molecular Mechanotransduction
 
 
 
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Contact

 

+44 (0)20 7594 5187a.del-rio-hernandez

 
 
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Location

 

308Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mehta:2020:10.1038/s41586-020-1979-4,
author = {Mehta, V and Pang, K-L and Rozbesky, D and Nather, K and Keen, A and Lachowski, D and Kong, Y and Karia, D and Ameismeier, M and Huang, J and Fang, Y and del, Rio Hernandez A and Reader, JS and Jones, EY and Tzima, E},
doi = {10.1038/s41586-020-1979-4},
journal = {Nature},
pages = {290--295},
title = {The guidance receptor plexin D1 is a mechanosensor in endothelial cells},
url = {http://dx.doi.org/10.1038/s41586-020-1979-4},
volume = {578},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Shear stress on arteries produced by blood flow is important for vascular development and homeostasis but can also initiate atherosclerosis1. Endothelial cells that line the vasculature use molecular mechanosensors to directly detect shear stress profiles that will ultimately lead to atheroprotective or atherogenic responses2. Plexins are key cell-surface receptors of the semaphorin family of cell-guidance signalling proteins and can regulate cellular patterning by modulating the cytoskeleton and focal adhesion structures3,4,5. However, a role for plexin proteins in mechanotransduction has not been examined. Here we show that plexin D1 (PLXND1) has a role in mechanosensation and mechanically induced disease pathogenesis. PLXND1 is required for the response of endothelial cells to shear stress in vitro and in vivo and regulates the site-specific distribution of atherosclerotic lesions. In endothelial cells, PLXND1 is a direct force sensor and forms a mechanocomplex with neuropilin-1 and VEGFR2 that is necessary and sufficient for conferring mechanosensitivity upstream of the junctional complex and integrins. PLXND1 achieves its binary functions as either a ligand or a force receptor by adopting two distinct molecular conformations. Our results establish a previously undescribed mechanosensor in endothelial cells that regulates cardiovascular pathophysiology, and provide a mechanism by which a single receptor can exhibit a binary biochemical nature.
AU  - Mehta,V
AU  - Pang,K-L
AU  - Rozbesky,D
AU  - Nather,K
AU  - Keen,A
AU  - Lachowski,D
AU  - Kong,Y
AU  - Karia,D
AU  - Ameismeier,M
AU  - Huang,J
AU  - Fang,Y
AU  - del,Rio Hernandez A
AU  - Reader,JS
AU  - Jones,EY
AU  - Tzima,E
DO  - 10.1038/s41586-020-1979-4
EP  - 295
PY  - 2020///
SN  - 0028-0836
SP  - 290
TI  - The guidance receptor plexin D1 is a mechanosensor in endothelial cells
T2  - Nature
UR  - http://dx.doi.org/10.1038/s41586-020-1979-4
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000511285700010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41586-020-1979-4
UR  - http://hdl.handle.net/10044/1/92397
VL  - 578
ER  -
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