Imperial College London
Alternate

ProfessorJuliaGorelik

Faculty of Medicine, National Heart & Lung Institute

Professor of Cellular Biophysics
 
 
 
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Contact

 

+44 (0)20 7594 2736j.gorelik Website

 
 
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Assistant

 

Miss Cheryl Costello +44 (0)20 7594 3001

 
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Location

 

429ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Schobesberger:2020:10.7554/eLife.52221,
author = {Schobesberger, S and Wright, PT and Poulet, C and Mardones, JLSA and Mansfield, C and Friebe, A and Harding, SE and Balligand, J-L and Nikolaev, VO and Gorelik, J},
doi = {10.7554/eLife.52221},
journal = {eLife},
pages = {1--15},
title = {beta(3)-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes},
url = {http://dx.doi.org/10.7554/eLife.52221},
volume = {9},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cardiomyocyte β3-adrenoceptors (β3-ARs) coupled to soluble guanylyl cyclase (sGC)-dependent production of the second messenger 3’,5’-cyclic guanosine monophosphate (cGMP) have been shown to protect from heart failure. However, the exact localization of these receptors to fine membrane structures and subcellular compartmentation of β3-AR/cGMP signals underpinning this protection in health and disease remain elusive. Here, we used a Förster Resonance Energy Transfer (FRET)-based cGMP biosensor combined with scanning ion conductance microscopy (SICM) to show that functional β3-ARs are mostly confined to the T-tubules of healthy rat cardiomyocytes. Heart failure, induced via myocardial infarction, causes a decrease of the cGMP levels generated by these receptors and a change of subcellular cGMP compartmentation. Furthermore, attenuated cGMP signals led to impaired phosphodiesterase two dependent negative cGMP-to-cAMP cross-talk. In conclusion, topographic and functional reorganization of the β3-AR/cGMP signalosome happens in heart failure and should be considered when designing new therapies acting via this receptor.
AU  - Schobesberger,S
AU  - Wright,PT
AU  - Poulet,C
AU  - Mardones,JLSA
AU  - Mansfield,C
AU  - Friebe,A
AU  - Harding,SE
AU  - Balligand,J-L
AU  - Nikolaev,VO
AU  - Gorelik,J
DO  - 10.7554/eLife.52221
EP  - 15
PY  - 2020///
SN  - 2050-084X
SP  - 1
TI  - beta(3)-Adrenoceptor redistribution impairs NO/cGMP/PDE2 signalling in failing cardiomyocytes
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.52221
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000525352700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://elifesciences.org/articles/52221
UR  - http://hdl.handle.net/10044/1/78622
VL  - 9
ER  -
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