In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease
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In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease. / Sprenger, Julia U; Perera, Ruwan K; Steinbrecher, Julia H; Lehnart, Stephan E; Maier, Lars S; Hasenfuss, Gerd; Nikolaev, Viacheslav O.
in: NAT COMMUN, Jahrgang 6, 04.2015, S. Art. 6965.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - In vivo model with targeted cAMP biosensor reveals changes in receptor-microdomain communication in cardiac disease
AU - Sprenger, Julia U
AU - Perera, Ruwan K
AU - Steinbrecher, Julia H
AU - Lehnart, Stephan E
AU - Maier, Lars S
AU - Hasenfuss, Gerd
AU - Nikolaev, Viacheslav O
PY - 2015/4
Y1 - 2015/4
N2 - 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 biocompatibility 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 phosphodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced β-adrenergic receptor-cAMP signalling to SERCA.
AB - 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 biocompatibility 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 phosphodiesterase-dependent receptor-microdomain communication, which is affected in hypertrophy, resulting in reduced β-adrenergic receptor-cAMP signalling to SERCA.
U2 - 10.1038/ncomms7965
DO - 10.1038/ncomms7965
M3 - SCORING: Journal article
C2 - 25917898
VL - 6
SP - Art. 6965
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
ER -