In vivo generation of an adenylylcyclase isoform with a half-molecule motif.

A truncated form of adenylylcyclase (type V-alpha) has been cloned from a cardiac cDNA library. It constitutes a half-molecule of type V adenylylcyclase diverging at the end of the first cytoplasmic loop. Northern blotting study has revealed the presence of such a mRNA species (approximately 3.5 kilobases in size) in the heart. Genomic sequence analysis has revealed that type V-alpha is generated via usage of a polyadenylation signal located within an intronic sequence of type V adenylylcyclase gene. When type V-alpha is co-expressed with an artificially generated half-molecule constituting the latter half of type V adenylylcyclase, the catalytic activity in transfected cell membranes is significantly higher than that of controls. However, when either alone is overexpressed, no significant increase in catalytic activity results. These results indicate that a half-molecule of adenylylcyclase, i.e. a protein containing six-transmembrane spans followed by a single cytoplasmic domain, can be generated in vivo, but catalytic activity is lacking unless heterodimerization can occur. This finding identifies another potential mechanism for generating diversity within this enzyme family.