Methods to investigate arrestins in complex with phosphodiesterases

Tibbo, A. J., Busiau, T. and Baillie, G. S. (2019) Methods to investigate arrestins in complex with phosphodiesterases. In: Scott, M. G.H. and Laporte, S. A. (eds.) Beta-Arrestins. Series: Methods in molecular biology (1957). Springer: New York, pp. 121-137. (doi: 10.1007/978-1-4939-9158-7_8)

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The many functions of β-arrestin proteins in the desensitization of G-protein-coupled receptors have been well characterized; however, the discovery that this scaffold protein could actually recruit phosphodiesterases (PDEs) to the site of cAMP synthesis changed the way researchers thought about the static nature of precisely localized cAMP hydrolysis by anchored PDEs. Before this discovery, the compartmentalization of cAMP gradients formed by the activation of specific receptors was generally understood to be underpinned by highly localized pools of specific PDEs that were anchored by large static anchors such as A-kinase-anchoring proteins (AKAPs). Such anchors acted to position cAMP effector proteins such as protein kinase A (PKA) and exchange protein directly activated by cAMP (EPAC) in places that would allow cAMP concentrations to breach their activation threshold only when a specific receptor activation occurred. In this arrangement PDEs acted as local "sinks" for cAMP and this enforced receptor-specific function by allowing the correct activation of a distinct pool of cAMP effectors in precise localizations. The discovery that β-arrestin could shuttle cAMP hydrolyzing activity to the membrane shortly after receptor activation added to the complexity of this process by restricting cAMP diffusion into the cell interior for some receptors. This chapter describes the methods used to identify, confirm, and test the function of PDE-β-arrestin complexes.

Item Type:Book Sections
Keywords:Arrestin, PDE, PKA, cAMP.
Glasgow Author(s) Enlighten ID:Tibbo, Dr Amy and Busiau, Miss Tara and Baillie, Professor George
Authors: Tibbo, A. J., Busiau, T., and Baillie, G. S.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health

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