Aneural origin of Ionotropic glutamate receptor signalling – OriSigNe

Ionotropic glutamate receptors (iGluRs) play a fundamental role in the central nervous system of Vertebrates as exclusive effectors of fast glutamatergic neurotransmission, in ?80% of the synapses of the brain. However recent studies revealed that some glutamate-insensitive orphan iGluRs are the effector a glycine-dependant excitatory signalling. This tonic glycine signalling appears important for proper brain functionning in Mammals but its role and origin remain poorly understood. iGluR genes can be found in all neural species from Cnidarian to Vertebrates. In a recent analysis of Eukaryotes iGluR phylogeny, we showed that glycine likely constitutes the most widespread agonist of Metazoan iGluRs. This also suggests that iGluR glycine signalling was already present in pre-neural Metazoans before the emergence of the nervous system.
Our project aims at exploring key steps of the origin and evolution of iGluR signalling using representative model species. We will establish the role and function of glycinergic iGluRs in a Cnidaria (neural Metazoans with no CNS) ; we will characterize the importance and mechanism of this paracrine signalling in a Sponge (an ancient branch of aneural Metazoans) ; finally we will study its environmental origin in an unicellular Algae (Diatom). Combining functional characterization of selected iGluR homologs, in silico agonist prediction and phenotypic tests on our model species, we will precise the molecular, cellular and evolutive landscape of iGluR signalling. Following more than 600 Mya of iGluR molecular co-evolution with the nervous system opens-up unprecedented perspectives for the understanding of our present brain function and development.