Sprenger, Julia U. and Perera, Ruwan K. and Steinbrecher, Julia H. and Lehnart, Stephan E. and Maier, Lars S. and Hasenfuss, Gerd and Nikolaev, Viacheslav O. (2015) In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease. NATURE COMMUNICATIONS, 6: 6965. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SARCOPLASMIC-RETICULUM; HEART-FAILURE; TRANSGENIC MICE; COMPARTMENTALIZED CAMP; SCAFFOLDING PROTEINS; CYCLIC-AMP; CARDIOMYOCYTES; KINASE; CGMP; PHOSPHODIESTERASES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jul 2019 12:51 |
| Last Modified: | 22 Jul 2019 12:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5696 |
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