The catecholamines up (Catsup) protein of Drosophila melanogaster functions as a negative regulator of tyrosine hydroxylase activity

We report the genetic, phenotypic, and biochemical analyses of Catecholamin es up (Catsup), a gene that encodes a negative regulator of tyrosine hydrox ylase (TH) activity. Mutations within this locus are semidominant lethals o f variable penetrance that result in three broad, overlapping effective let hal phases (ELPs), indicating that the Catsup gene product is essential thr oughout development. Mutants from each ELF exhibit either cuticle defects o r catecholamine-related abnormalities, such as melanotic salivary glands or pseudotumors. Additionally, Catsup mutants have significantly elevated TH activity that may arise from a post-translational modification of the enzym e. The hyperactivation of TH in Catsup mutants results in abnormally high l evels of catecholamines, which can account for the lethality, visible pheno types, and female sterility observed in these mutants. We propose that Cats up is a component of a novel system that downregulates TH activity, making Catsup the fourth locus found within the Dopa decarboxylase (Ddc) gene clus ter that functions in catecholamine metabolism.