In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease
2015 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease
Sprenger, J. U.; Perera, R. K. ; Steinbrecher, J. H.; Lehnart, S. E. ; Maier, L. S. ; Hasenfuß, G. & Nikolaev, V. O. (2015)
Nature Communications, 6 art. 6965. DOI: https://doi.org/10.1038/ncomms7965
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- Authors
- Sprenger, Julia U.; Perera, Ruwan K. ; Steinbrecher, Julia H.; Lehnart, Stephan E. ; Maier, Lars S. ; Hasenfuß, Gerd ; Nikolaev, Viacheslav O.
- Abstract
- 3',5'-cyclic adenosine monophosphate (cAMP) is an ubiquitous second messenger that regulates physiological functions by acting in distinct subcellular microdomains. Although several targeted cAMP biosensors are developed and used in single cells, it is unclear whether such biosensors can be successfully applied in vivo, especially in the context of disease. Here, we describe a transgenic mouse model expressing a targeted cAMP sensor and analyse microdomain-specific second messenger dynamics in the vicinity of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). We demonstrate the bio-compatibility of this targeted sensor and its potential for real-time monitoring of compartmentalized cAMP signalling in adult cardiomyocytes isolated from a healthy mouse heart and from an in vivo cardiac disease model. In particular, we uncover the existence of a phos-phodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced beta-adrenergic receptor-cAMP signalling to SERCA.
- Issue Date
- 2015
- Journal
- Nature Communications
- Project
- SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz
SFB 1002 | A01: cAMP- und cGMP- Mikrodomänen bei Herzhypertrophie und Insuffizienz
SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion - Working Group
- RG Hasenfuß (Transition zur Herzinsuffizienz)
RG L. Maier (Experimentelle Kardiologie)
RG Nikolaev (Cardiovascular Research Center)
RG Lehnart (Cellular Biophysics and Translational Cardiology Section) - ISSN
- 2041-1723