<i>nemy</i> encodes a cytochrome b561 that is required for <i>Drosophila</i> learning and memory

Abstract

Although many genes have been shown to play essential roles in learning and memory, the precise molecular and cellular mechanisms underlying these processes remain to be fully elucidated. Here, we present the molecular and behavioral characterization of the Drosophila memory mutant nemy. We provide multiple lines of evidence to show that nemy arises from a mutation in a Drosophila homologue of cytochrome B561. nemy is predominantly expressed in neuroendocrine neurons in the larval brain, and in mushroom bodies and antennal lobes in the adult brain, where it is partially coexpressed with peptidyl alpha-hydroxylating monooxygenase (PHM), an enzyme required for peptide amidation. Cytochrome b561 was found to be a requisite cofactor for PHM activity and we found that the levels of amidated peptides were reduced in nemy mutants. Moreover, we found that knockdown of PHM gave rise to defects in memory retention. Altogether, the data are consistent with a model whereby cytochrome B561-mediated electron transport plays a role in memory formation by regulating intravesicular PHM activity and the formation of amidated neuropeptides.