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Sci. Signal., 10 April 2012
Vol. 5, Issue 219, p. ra29
Bound to Signal in Close Quarters
Interplay between the calcium and the cyclic adenosine monophosphate (cAMP) signaling pathways is crucial to numerous physiological events. Although membrane-bound calcium-sensitive adenylyl cyclases (ACs) are sensitive to submicromolar concentrations of calcium in vitro, in cells they are highly selective in responding to store-operated calcium (SOC) entry rather than to calcium released from intracellular stores or entering the cell through ionophores. Here, Willoughby et al. used a combination of live-cell imaging techniques and biochemical approaches to resolve this conundrum and showed that AC8, which is stimulated by calcium-bound calmodulin, forms a direct protein-protein interaction with Orai1, the pore-forming component of the channel that mediates SOC entry. The existence of AC8 in a complex with SOC channels provides a mechanism for the compartmentalized regulation of cAMP signaling by specific subcellular calcium signals.
Citation: D. Willoughby, K. L. Everett, M. L. Halls, J. Pacheco, P. Skroblin, L. Vaca, E. Klussmann, D. M. F. Cooper, Direct Binding Between Orai1 and AC8 Mediates Dynamic Interplay Between Ca2+ and cAMP Signaling. Sci. Signal.5, ra29 (2012).
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