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Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling

Item Type:Article
Title:Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling
Creators Name:Willoughby, D. and Everett, K.L. and Halls, M.L. and Pacheco, J. and Skroblin, P. and Vaca, L. and Klussmann, E. and Cooper, D.M.
Abstract:The interplay between calcium ion (Ca(2+)) and cyclic adenosine monophosphate (cAMP) signaling underlies crucial aspects of cell homeostasis. The membrane-bound Ca(2+)-regulated adenylyl cyclases (ACs) are pivotal points of this integration. These enzymes display high selectivity for Ca(2+) entry arising from the activation of store-operated Ca(2+) (SOC) channels, and they have been proposed to functionally colocalize with SOC channels to reinforce crosstalk between the two signaling pathways. Using a multidisciplinary approach, we have identified a direct interaction between the amino termini of Ca(2+)-stimulated AC8 and Orai1, the pore component of SOC channels. High-resolution biosensors targeted to the AC8 and Orai1 microdomains revealed that this protein-protein interaction is responsible for coordinating subcellular changes in both Ca(2+) and cAMP. The demonstration that Orai1 functions as an integral component of a highly organized signaling complex to coordinate Ca(2+) and cAMP signals underscores how SOC channels can be recruited to maximize the efficiency of the interplay between these two ubiquitous signaling pathways.
Keywords:Adenylate Cyclase, Bacterial Proteins, Calcium, Calcium Channels, Cyclic AMP, Fluorescence Resonance Energy Transfer, HEK293 Cells, Homeostasis, Ions, Luminescent Proteins, Tertiary Protein Structure
Source:Science Signaling
ISSN:1937-9145
Publisher:American Association for the Advancement of Science (U.S.A.)
Volume:5
Number:219
Page Range:ra29
Date:10 April 2012
Official Publication:https://doi.org/10.1126/scisignal.2002299
PubMed:View item in PubMed

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