Soluble Adenylate Cyclase 1

The cellular levels of Cyclic AMP (cAMP), a key messenger in several signal transduction pathways, are maintained by the orchestrated activities of two opposing enzymes: synthesizing Adenylyl cyclases (AC) and hydrolyzing phosphodiesterases (PDEs).  The synthesizing enzymes (ACs) are found in two forms: cytosolic (soluble) and membrane-bound (particulate).  In all 9 particulate AC have been characterized so far.  In last several years new members of particulate Adenylate cyclase family have been identified and significant progress is made in understanding the molecular mechanisms that underlie the regulation of this family of enzymes.  In response to G-protein couple’s receptor stimultion, the cAMP can be produced from ATP by either cytoplasmic or particulate AC. 

"Soluble" adenylyl cyclase (SAC) is a widely expressed mainly in mammalian cells that is evolutionarily, structurally, and biochemically distinct from the G protein-responsive transmembrane adenylyl cyclases.  The SAC are contrary to PAC, are insensitive to heterotrimeric G protein regulation and forskolin stimulation and is uniquely modulated by bicarbonate ions (1).  The SAC are distributed in specific sub cellular compartments (mitochondria, centrioles, mitotic spindles, mid-bodies, and nuclei, all of which contain cAMP targets). Distribution at these intracellular sites proves that adenylyl cyclases are in close proximity to all cAMP effectors, suggesting a model in which local concentrations of cAMP are regulated by individual adenylyl cyclases targeted to specific microdomains throughout the cell (2).  Two different transcripts produced RT-PCR and RNAse protection assays, encoding a full-length and truncated sAC were identified.  The smaller SAC transcript lacks exon 11 with a premature termination of the open reading frame after the catalytic domain and is expressed in the germ cells of the testis (3).  These transcripts were absent at age 11days but appear between 20-30 days of age in rat testis and are present through out adult life.   

For research use only, not for diagnostic or therapeutic use.