Altered autophosphorylation of adenosine 3',5'-phosphate-dependent protein kinase in the dunce memory mutant of Drosophila melanogaster.

The phosphorylation-dephosphorylation, in the presence of adenosine 5'-[gamma-32P]triphosphate, of a polypeptide of apparent molecular mass 53,000 has been compared in head homogenates of wild type and memory mutant dunceM11 strains of Drosophila melanogaster. In both strains, labelling of the 53 kilodalton protein required exogenous adenosine 3',5'-phosphate (cAMP), but in dunceM11 cAMP at higher concentration (above approximately 3 microM) caused the rapid disappearance of the label. This differential dephosphorylation can be attributed to the lack of a cAMP-specific phosphodiesterase isoenzyme in the mutant. Several lines of evidence indicate that the 53 kilodalton protein is identical with the regulatory subunit of cAMP-dependent protein kinase. The findings suggest that in the mutant's nerve cells the state of phosphorylation of the regulatory subunit of cAMP-dependent protein kinase is altered, which may contribute to the biochemical disorder leading to the memory deficit.