title: Organization of cAMP signalling microdomains for optimal regulation by Ca2+ entry.
abstract: Cross-talk between cAMP and Ca2+ signalling pathways plays a critical role in cellular homoeostasis. Several AC (adenylate cyclase) isoforms, catalysing the production of cAMP from ATP, display sensitivity to submicromolar changes in intracellular Ca2+ and, as a consequence, are key sites for Ca2+ and cAMP interplay. Interestingly, these Ca2+-regulated ACs are not equally responsive to equivalent Ca2+ rises within the cell, but display a remarkable selectivity for regulation by SOCE (store-operated Ca2+ entry). Over the years, considerable efforts at investigating this phenomenon have provided indirect evidence of an intimate association between Ca2+-sensitive AC isoforms and sites of SOCE. Now, recent identification of the molecular components of SOCE [namely STIM1 (stromal interaction molecule 1) and Orai1], coupled with significant advances in the generation of high-resolution targeted biosensors for Ca2+ and cAMP, have provided the first detailed insight into the organization of the cellular microdomains associated with Ca2+-regulated ACs. In the present review, I summarize the findings that have helped to provide our most definitive understanding of the selective regulation of cAMP signalling by SOCE.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. dw212@cam.ac.uk
authors.forename: Debbie
authors.initials: D
authors.lastname: Willoughby
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D046912:Multiprotein Complexes / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015220:Calcium Channels; D046912:Multiprotein Complexes; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium