RESUMEN
nalyot (nal) is a novel olfactory memory mutant of Drosophila, encoding Adf1, a myb-related transcription factor. Following extended training sessions, Adf1 mutants show normal early memory but defective longterm memory. Adf1 shows widespread spatiotemporal expression, yet mutant alleles reveal no discernible disruptions in gross morphology of the nervous system. Studies at the larval neuromuscular junction, however, reveal a role for Adf1 in the modulation of synaptic growth-in contrast to the role established for dCREB2 in the control of synaptic function (Davis et al., 1996). These findings suggest that Adf1 and dCREB2 regulate distinct transcriptional cascades involved in terminal stages of synapse maturation. More generally, Adf1 provides a novel link between molecular mechanisms of developmental and behavioral plasticity.
Asunto(s)
Proteínas de Drosophila , Genes myb/genética , Proteínas de Insectos/genética , Memoria/fisiología , Mutación/genética , Mutación/fisiología , Olfato/genética , Olfato/fisiología , Sinapsis/fisiología , Factores de Transcripción/genética , Factor de Transcripción Activador 4 , Alelos , Animales , Northern Blotting , Western Blotting , Condicionamiento Clásico/fisiología , Sondas de ADN , Drosophila , Electrofisiología , Embrión no Mamífero , Regulación de la Expresión Génica/fisiología , Proteínas de Insectos/biosíntesis , Larva , Leucina Zippers , Sistema Nervioso/crecimiento & desarrollo , Unión Neuromuscular/fisiología , Terminales Presinápticos/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/metabolismoRESUMEN
Disruptions of a Drosophila gene encoding a regulatory subunit of cAMP-dependent protein kinase homologous to mammalian RIbeta (dPKA-RI) were targeted to the first (noncoding) exon of dPKA-RI via site-selected P element mutagenesis. Flies homozygous for either of two mutant alleles showed specific defects in olfactory learning but not in subsequent memory decay. In contrast, olfactory acuity and shock reactivity, component behaviors required for normal odor avoidance learning, were normal in these mutants. Northern and Western blot analyses of mRNA and protein extracted from adult heads have revealed a complex lesion of the PKA-RI locus, including expression of a novel product and over- or underexpression of wild-type products in mutants. Western blot analysis revealed reductions in RI protein in mutants. PKA activity in the absence of exogenous cAMP also was significantly higher than normal in homogenates from mutant adult heads. These two mutant alleles failed to complement each other for each of these phenotypic defects, eliminating second-site mutations as a possible explanation. These results establish a role for an RI regulatory subunit of PKA in Pavlovian olfactory conditioning.