Characterisation of human adenylyl cyclase IX reveals inhibition by Ca(2+)/Calcineurin and differential mRNA plyadenylation.
The functional diversity of adenylyl cyclases provides for different modes of cyclic AMP signalling in mammals. This study reports the cloning and functional characterisation of a cDNA encoding human adenylyl cyclase IX (ACIX). The data show that human ACIX is a Ca(2+)/calcineurin-inhibited adenylyl cyclase prominently expressed in vital organs, including brain, heart, and pancreas. ACIX mRNA was detected in several brain regions, including neocortex, hippocampus, striatum, and cerebellum. By in situ hybridisation, ACIX mRNA was localised to pyramidal and granule cells of the hippocampus, indicating that it is expressed predominantly in nerve cells. Further analysis of ACIX mRNA expression revealed two major forms of ACIX mRNA that arose through tissue-specific differential mRNA polyadenylation. Taken together, the data show that (a) human ACIX is under inhibitory control by Ca(2+) through calcineurin, (b) ACIX may be involved in higher brain functions, and (c) post-transcriptional regulation of ACIX gene expression is a species-specific control mechanism that may enhance the versatility of cyclic AMP signalling in humans.
Paterson
J M
JM
MRC Brain Metabolism Unit, Department of Neuroscience, Western General Hospital, University of Edinburgh, Edinburgh, Scotland. Janice.Paterson@ed.ac.uk
Smith
S M
SM
Simpson
J
J
Grace
O C
OC
Sosunov
A A
AA
Bell
J E
JE
Antoni
F A
FA
D020413:3' Untranslated Regions / Q000235:genetics; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism* / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D016548:Prosencephalon / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D020413:3' Untranslated Regions; D000067956:Adenylyl Cyclase Inhibitors; D065095:Calcineurin Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D000242:Cyclic AMP; D019703:Calcineurin; D000262:Adenylyl Cyclases; C413923:adenylate cyclase 9; D002118:Calcium