Premium
Characterisation of Human Adenylyl Cyclase IX Reveals Inhibition by Ca 2+ /Calcineurin and Differential mRNA Plyadenylation
Author(s) -
Paterson Janice M.,
Smith Susan M.,
Simpson James,
Grace O. Cathal,
Sosunov Alexander A.,
Bell Jeanne E.,
Antoni Ferenc A.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751358.x
Subject(s) - adenylyl cyclase , calcineurin , adcy10 , biology , messenger rna , adcy9 , neocortex , microbiology and biotechnology , signal transduction , medicine , biochemistry , gene , neuroscience , transplantation
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.