Growth regulation by GTP. Regulation of nucleotide pools in Neurospora by nitrogen and sulfur control systems

Purine nucleotide pools in the fungus Neurospora crassa decline in response to carbon, nitrogen, or sulfur deprivation. There is, in addition, a decline in GTP/ATP ratios on nitrogen or sulfur deprivation in wild type. The GTP/ATP decline is missing on nitrogen deprivation of the nitrogen control mutant, nit-2, and on sulfur deprivation of the sulfur control mutant, cys-3. The nit-2 mutant also shows elevated UTP pools on nitrogen deprivation when compared with similarly treated wild type. Six-hour sulfur-deprived cys-3 shows multiple aberrations in nucleotide pools when compared with similarly treated wild type. These include very low energy charge and depletion of pools of most nucleotides. ATP in sulfur-deprived cys-3 drops by about 88%. Sulfur-deprived cys-3 is also greatly impaired in comparison with wild type in its ability to resume growth when restored to nutritional sufficiency after a period of sulfur deprivation. These results clearly demonstrate that the nitrogen (nit-2) and sulfur (cys-3 regulatory systems are not limited to control of catabolism of exogenous nitrogen and sulfur sources, respectively, but rather influence, a broader range of cellular properties than has been previously thought. The pattern of GTP pool control is consistent with a positive role for GTP in growth control. Evidence in other systems supporting such a growth-regulating role for GTP is discussed.