Molecular and cellular requirements for the regulation of adenylate cyclases by calcium.
Calcium-sensitive adenylate cyclases provide a key regulatory device for integrating the activities of the two major signalling systems, Ca(2+) and cAMP. Recent experiments have brought us closer to understanding the molecular mechanisms whereby Ca(2+) either stimulates or inhibits susceptible adenylate cyclases in vitro. However, in the intact cell an additional layer of sophistication is evident whereby Ca(2+)-sensitive adenylate cyclases are juxtaposed with Ca(2+)-entry channels, such that the cyclases respond selectively to capacitative Ca(2+) entry. Part of this dependency is enforced by the placement of Ca(2+)-sensitive adenylate cyclases (AC5, AC6 and AC8) in caveolae, from which at least one Ca(2+)-insensitive adenylate cyclase (AC7) is excluded. However, additional protein-protein interactions are also required to ensure the dependency of these cyclases on capacitative Ca(2+) entry. Recent findings in this area and their implications for 'local cAMP signals' will be discussed.
D000262:Adenylyl Cyclases / Q000096:biosynthesis*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D021962:Membrane Microdomains / Q000201:enzymology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium