Defective responsiveness of adenylate cyclase to forskolin in the Drosophila memory mutant rutabaga.
The Drosophila memory mutant rutabaga (rut) has been previously shown to have a defective subpopulation (or functional state) of the enzyme adenylate cyclase. We report here that the reduced adenylate cyclase activity is also associated with a defective responsiveness of the enzyme to forskolin. Forskolin activation isotherms of the enzyme in normal membranes reveal low- and high-affinity forskolin-interacting components; the residual enzyme in the mutant shows a smaller proportion of the high-affinity response. In addition, in mutant membrane preparations, forskolin fails to shift the Km of the enzyme for free Mg2+ and for MgATP, in contrast to the situation in the normal tissue. The defect in the responsiveness to forskolin in rut is even more pronounced in a Lubrol-solubilized enzyme preparation, and is due to intrinsic properties of the cyclase system rather than to the absence (or presence) of a soluble, or detergent solubilized, factor in rut. The reduced forskolin responsiveness maps to the X chromosomal segment 12F5-6 to 13A1-5, within the region previously reported to span the locus that controls both the abortive memory and the lack of Ca2+-stimulation of adenylate cyclase in rut17. The possible relevance of the findings to postulated molecular mechanisms of short-term memory formation is discussed.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002874:Chromosome Mapping; D005576:Colforsin / Q000494:pharmacology*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008566:Membranes / Q000201:enzymology; D008568:Memory / Q000502:physiology*; D009655:Octopamine / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D013873:Thionucleotides; D009655:Octopamine; D005576:Colforsin; D014268:Trifluoperazine; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D000262:Adenylyl Cyclases; D008274:Magnesium