title: Cyclic adenosine monophosphate metabolism in synaptic growth, strength, and precision: neural and behavioral phenotype-specific counterbalancing effects between dnc phosphodiesterase and rut adenylyl cyclase mutations.
abstract: Two classic learning mutants in Drosophila, rutabaga (rut) and dunce (dnc), are defective in cyclic adenosine monophosphate (cAMP) synthesis and degradation, respectively, exhibiting a variety of neuronal and behavioral defects. We ask how the opposing effects of these mutations on cAMP levels modify subsets of phenotypes, and whether any specific phenotypes could be ameliorated by biochemical counter balancing effects in dnc rut double mutants. Our study at larval neuromuscular junctions (NMJs) demonstrates that dnc mutations caused severe defects in nerve terminal morphology, characterized by unusually large synaptic boutons and aberrant innervation patterns. Interestingly, a counterbalancing effect led to rescue of the aberrant innervation patterns but the enlarged boutons in dnc rut double mutant remained as extreme as those in dnc. In contrast to dnc, rut mutations strongly affect synaptic transmission. Focal loose-patch recording data accumulated over 4 years suggest that synaptic currents in rut boutons were characterized by unusually large temporal dispersion and a seasonal variation in the amount of transmitter release, with diminished synaptic currents in summer months. Experiments with different rearing temperatures revealed that high temperature (29-30°C) decreased synaptic transmission in rut, but did not alter dnc and wild-type (WT). Importantly, the large temporal dispersion and abnormal temperature dependence of synaptic transmission, characteristic of rut, still persisted in dnc rut double mutants. To interpret these results in a proper perspective, we reviewed previously documented differential effects of dnc and rut mutations and their genetic interactions in double mutants on a variety of physiological and behavioral phenotypes. The cases of rescue in double mutants are associated with gradual developmental and maintenance processes whereas many behavioral and physiological manifestations on faster time scales could not be rescued. We discuss factors that could contribute to the effectiveness of counterbalancing interactions between dnc and rut mutations for phenotypic rescue.
authors.affiliation: Department of Biology, University of Iowa, IA 52242, USA. atushi-ueda@uiowa.edu
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ueda
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C523245:dnc protein, Drosophila; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C479926:Rut protein, Drosophila