dunce

Targets of Activity

DCO, the catalytic subunit of Protein kinase A, is preferentially expressed in the mushroom bodies. PKA is the target of cAMP, degraded through enzymatic activity of the Dunce protein. PKA is a heterotetramer, consisting of two subunits of DC0 and two subunits of a regulatory subunit. Binding of cAMP to the regulatory subunits causes them to dissociate from the tetramer, activating PKA enzymatic activity. Mutants for DCO produce homozygous lethality and a 40% decrease in PKA activity in heterozygotes. This decrease has mild effects on learning but no effect on memory. However, the 80% reduction in activity obtained by constructing double mutant heteroallelic viable animals results in a dramatic learning and memory deficit. These results suggest that PKA plays a crucial role in the cAMP cascade in mushroom bodies to mediate learning and memory processes (Skoulakis, 1993).

There are several genes expressed at abnormal levels in the memory mutant, dunce. These mutants have an elevated cyclic AMP (cAMP) content due to a mutation in the structural gene for cAMP phosphodiesterase, so the isolated genes are potentially those regulated by cAMP. There are two uninterrupted and complete open reading frames (SER1 and SER2) and part of a third (SER3), all found to be homologous to the serine protease family of enzymes. Only the SER1-related genes were differentially expressed in dnc mutants. The putative serine protease genes are abundantly expressed in the larval gut, suggesting a major function in digestion. Feeding normal flies cAMP, isobutylmethylxanthine, or forskolin results in a decreased RNA level of the SER1-related genes. Thus, RNA levels of this serine protease gene family are negatively regulated through cAMP (Yun, 1989).

Home page: The Interactive Fly © 1997 Thomas B. Brody, Ph.D.

The Interactive Fly resides on the
Society for Developmental Biology's Web server.