Resumen del póster presentado al 22nd IUBMB & 37th FEBS Congress: "From Single Molecules to Systems Biology" celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012. NLaz (Neural Lazarillo) is a glycoprotein secreted mainly by neurons in Drosophila. As a member of the Lipocalin family, NLaz is expected to form an eight-strand b-barrel with a hydrophobic binding pocket. Despite being probably a key element for its function, no physiological ligand has been reported for NLaz. We show that NLaz binds in vitro ergosterol and 7(z)-tricosene in the micromolar range. A point mutation (L130R) in NLaz pocket compromises ligand binding. NLaz is involved in longevity by inhibition of the insulin signaling (IIS) pathway. Its human closest homologue, Apolipoprotein D (ApoD) shows a robust and evolutionarily conserved upregulation with age in the brain. NLaz loss-of-function (KO) fly mutants have reduced longevity and are hypersensitive to stress. Overexpressing NLaz rescues the NLaz-KO phenotype upon exposure to oxidative or desiccationstress. However, a partial rescue is achieved by overexpressing the NLaz-L130R mutant. Moreover, NLaz-KO flies show altered mating behavior and a dramatically low courtship index. This phenotype is rescued by over-expression of NLaz-WT, but is partially rescued by the binding pocket-mutant NLaz-L130R. We conclude that NLaz ability to protect against oxidative stress and to regulate mating behavior is dependent on NLaz-ligand interactions. We are currently analyzing the expression profile in WT, KO and L130R NLaz flies. Genes involved in oxidative stress, metabolic responses including the IIS pathway, and pheromonal signaling will be explored in order to gain further insight into the importance of NLaz hydrophobic ligand-binding in the NLazdependent modulation of longevity and reproductive behaviors. Peer reviewed