Local cAMP dynamics in the SERCA2a signalling complex

TL;DRAbstract

3’,5’-cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger that regulates multiple physiological functions by acting in distinct subcellular microdomains. Over the last few years, several targeted biosensors have been developed and used in cell lines or neonatal cardiomyocytes to investigate the molecular mechanisms behind cAMP compartmentation. However, it is unclear whether such biosensors can be successfully used for expression in vivo, especially in the context of disease such as cardiac hypertrophy. Importantly, cAMP regulates cardiac function by acting in distinct subcellular microdomains which are independently regulated and confined from the bulk cytosol. Today, this phenomenon is a well accepted paradigm known as cAMP compartmentation. In the heart, one of these microdomains is believed to be located around the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a). SERCA2a is crucial for diastolic calcium (Ca2+) reuptake and is negatively regulated b

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