September 2015

This study published in Nature Communications deals with the messenger substance 3‘5‘-cyclic adenosine monophosphate (cAMP) and its local regulation in healthy and hypertrophic cardiomyocytes. cAMP exerts its physiological effects in so-called subcellular microdomains, whose functional visualization was not previously possible. A team of investigators led by Viacheslav Nikolaev from the Hamburg/Kiel/Lübeck partner site report on a new Förster resonance energy transfer (FRET)-based biosensor which, by virtue of its coupling to phospholamban, can directly visualize the subcellular cAMP dynamics in the SERCA2a microdomain - an important contributor to calcium cycling. The investigators used this sensor to generate the world’s first in vivo mouse model with a localized FRET biosensor. The advantage of this model is that measurements can be taken directly in freshly isolated healthy and pathological adult cardiomyocytes and, in the long term, also in intact hearts. These measurements demonstrated the existence of direct cAMP-dependent communication between β-adrenoceptors and the SERCA2a microdomain. This communication is regulated by specific cAMP-degrading enzymes (phosphodiesterases) and is dramatically impaired in cardiac hypertrophy. In summary, the researchers were able to use a localized FRET biosensor in vivo for the first time and thus gained new insights into the molecular mechanisms underlying cardiac hypertrophy.

Link to the Paper