Adenosine 3':5'-cyclic monophosphate deficiency in Neurospora crassa.
Depending on growth conditions, the adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels of the fr mutant, a morphologically aberrant strain of Neurospora crassa, are reduced 2- to 5-fold. By taking advantage of the differences in phenotype of fr in liquid and agar cultures and the positive response of fr grown on solid support to exogenous theophylline, a relationship between the degree of morphological abnormality and intracellular cyclic AMP levels of the mutant is observed. Progressive restoration of the fr phenotype toward a normal state is paralleled by increases in cyclic nucleotide content. Striking differences in the sedimentation and thermal characteristics of the fr and wild-type adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] are observed. Approximately 50% of the normal activity sediments at 105,000 X g compared to 5% of the mutant enzyme. In addition, the overall stability of the fr adenylate cyclase is significantly decreased and its rate of inactivation at 37 degrees in the absence of substrate is 10-fold greater than the wild-type adenylate cyclase. Arrhenius plots also indicated that the Q10 (increase in rate per 10 degrees temperature increase) and the temperature of maximal activity of the fr enzyme are reduced. Supplementation of fr agar cultures with linolenic acid results in an elevated cyclic AMP content and a wild-type-like morphology similar to that obtained with inhibitors of phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). An increased thermostability of the fr adenylate cyclase occurs on linolenate enrichment of the mutant. It is concluded that the cyclic AMP deficiency is at least partially responsible for the fr phenotype and that this reduction results from a membrane defect that affects adenylate cyclase function.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000628:Aminophylline / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D009154:Mutation; D009491:Neurospora / Q000378:metabolism*; D009492:Neurospora crassa / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D005231:Fatty Acids, Unsaturated; D000628:Aminophylline; D013806:Theophylline; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases