A role for glycine in the gating of plant NMDA-like receptors

The amino acid glycine has a well-established role in signalling in the mammalian central nervous system. For example, glycine acts synergistically with the major excitatory neurotransmitter, glutamate, to regulate the influx of ions such as calcium, through N-methyl-D-aspartate (NMDA) receptors. Plants possess NMDA-like receptors, generically referred to as glutamate receptors (GLRs), named on the basis of their presumed ligand, glutamate. Previously, glycine has not been implicated in plant GLR activity or any other aspect of plant signalling. Using transgenic Arabidopsis seedlings expressing aequorin to monitor ligand-mediated changes in the cytosolic concentration of Ca2+ ([Ca2+](cyt)), the data presented herein show that glutamate and glycine act synergistically to control ligand-mediated gating of calcium in plants. Glutamate and glycine synergism also regulates hypocotyl elongation. Transient increases in [Ca2+](cyt) mediated by glutamate and glycine, as well as hypocotyl elongation, were inhibited by 6,7-dinitroquinoxaline-2,3 dione (DNQX), a competitive inhibitor of animal GLRs. Using a multiscale docking algorithm in combination with a molecular model of the ligand-binding domain of plant GLRs, evidence is provided indicating that glycine, and not glutamate, is likely to be the natural ligand for most plant GLR subunits. These findings uncover a hitherto unconsidered role for glycine signalling in plants, and suggest that the synergistic action of glutamate and glycine at NMDA-like receptors predates the divergence of plants and animals.