Regulation of ryanodine receptor mediated perinuclear calcium by the mAKAP complex

Gildart, Moriah; Kapiloff, Michael S.; Dodge‐Kafka, Kimberly L.

doi:10.1016/j.yjmcc.2017.07.105

Cited by 1 publication

(1 citation statement)

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“…The fact that different phosphatases associate with individual signalosomes provides further complexity to the regulation of cAMP signals by enabling additional local variation in the signal dynamics. In the heart, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) catalyse between 70% and 90% of all dephosphorylation events [91], although protein phosphatase 2B (PP2B) (calcineurin, CaN) also contributes [92]. The number of phosphatases is significantly smaller than the number of targets they dephosphorylate and substrate specificity primarily relies on the role of regulatory subunit, which also dictate their subcellular localization [93].…”

Section: Phosphatasesmentioning

confidence: 99%

Compartmentalized cAMP signalling and control of cardiac rhythm

Tomek

Zaccolo

2023

Phil. Trans. R. Soc. B

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In the last 30 years, the field of cyclic adenosine 3′,5′-monophosphate (cAMP) signalling has witnessed a transformative development with the realization that cAMP is compartmentalized and that spatial regulation of cAMP is critical for faithful signal propagation and hormonal specificity. This recognition has changed our understanding of cAMP signalling from the canonical model, where a linear pathway connects a plasma membrane receptor to intracellular effectors and their targets, to a model where signal transduction occurs within a complex network of alternative branches and where an individual receptor leads to activation of a limited fraction of the network, enabled by local regulation of independent signalling units, resulting in a specific functional outcome. The cardiac myocyte has served as the cell model for many of the original findings leading to this paradigm. In this review, we cover some of the evidence supporting this new perspective and discuss how this model is providing novel mechanistic insight into cardiac myocyte physiology. With a focus on the regulation of cardiac rhythm, we consider how this model can provide an original framework for the identification of disease mechanisms. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.

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Section: Phosphatasesmentioning

confidence: 99%