GDP-mannose pyrophosphorylase is a genetic determinant of ammonium sensitivity in Arabidopsis thaliana

Higher plant species differ widely in their growth responses to ammonium (NH4+). However, the molecular genetic mechanisms underlying NH4+ sensitivity in plants remain unknown. Here, we report that mutations in the Arabidopsis gene encoding GDPmannose pyrophosphorylase (GMPase) essential for synthesizing GDP-mannose confer hypersensitivity to NH4+. The in planta activities of WT and mutant GMPases all were inhibited by NH4+, but the magnitude of the inhibition was significantly larger in the mutant. Despite the involvement of GDP-mannose in both L-ascorbic acid (ASA) and N-glycoprotein biosynthesis, defective protein glycosylation in the roots, rather than decreased ASA content, was linked to the hypersensitivity of GMPase mutants to NH4+. We conclude that NH4+ inhibits GMPase activity and that the level of GMPase activity regulates Arabidopsis sensitivity to NH4+. Further analysis showed that defective N-glycosylation of proteins, unfolded protein response, and cell death in the roots are likely important downstream molecular events involved in the growth inhibition of Arabidopsis by NH4+