Expression of adenylate cyclase and phosphodiesterase in development of temperature-sensitive mutants with impaired metabolism of cAMP in Drosophila melanogaster

The mode of the developmental expression of adenylate cyclase (AC) and phosphodiesterase (PDE) in D melanogaster indicates that PDE plays the major role in the maintenance of a certain level of cAMP in postembryonic development, while both enzymes function in concert in imago. The ts-mutants ts155 and ts622, characterized upon their isolation as having an increased cAMP content and normal PDE activity, manifest high levels of AC activity from the third day of imago life. The levels of PDE activity characteristic for adult mutants with altered enzyme activity (low in ts66 and ts980, high in ts398) are manifested in ts980 from larval instar II, and from the larval instar III in ts398 and ts66. Data on the dependence of PDE activity in adults upon temperature of incubation, being in agreement with the expectations for a ts-mutation in a gene coding for a form of PDE in case of ts66, suggest that ts398 affects not the enzyme-coding gene but rather one for an activator protein. The fact that in ts398 (the polyphasic ts-lethal mapping to 1-38.9) 1) AC activity is somewhat higher than normal at 22°C and is readily activated at 29°C, 2) activity of PDE-I assayed in heat-pretreated homogenates is higher than normal, 3) that boiled extracts of ts398 are potent activators of the wild type and of its own PDE-I indicates that it is a mutation affecting calmodulin, which is known to be stable at boiling and capable of activating both AC and PDE-I. Data on Ca2+ and EGTA effects suggest that the mutation presumably increases Ca2+-binding activity of calmodulin, ts980 and ts622, in which ts-lethality could be produced only by certain doses of haloperidol and triftazine, appear to be lethal in compounds with ts398, thus indicating that these mutations could affect the same calmodulin-controlling gene.