The role of glutamine synthetase and glutamine metabolism in nitrogen metabolite repression, a regulatory phenomenon in the lower eukaryote Neurospora crassa

Summary

Growth of Neurospora crassa on media containing NH ⁺₄ leads to the repression of a variety of permeases and alternative pathways which would generate NH ⁺₄ , so called “ammonium repression.” The mutant am ₂ which lacks NADP-GDH is not subject to ammonium repression of nitrate reductase or urea permease, but like the wild type has repressed levels of these systems when grown in the presence of proline, glutamate or glutamine. The glutamine synthetase (GS) mutant gln-la has derepressed levels of the aforementioned systems unless grown with glutamine.

The oligomeric state of GS depends upon the nitrogen sufficiency of the cell, a tetrameric form predominates under conditions of nitrogen limitation and an octameric form under conditions of nitrogen sufficiency. We have found that the tetrameric form GS predominates in the mutants am ₂ and gln-la when they are ammonium derepressed.

The mechanism of NH ⁺₄ repression in N. crassa is thought to entail a cessation of positive gene action by the product of the nit-2 regulatory gene. We propose that under conditions of NH ⁺₄ sufficiency, and hence glutamine sufficiency, the octameric form of GS represses nit-2 gene expression and thereby achieves ammonium repression.