Molecular basis of the differential interaction with lithium of glycine transporters GLYT1 and GLYT2

摘要: J. Neurochem. (2011) 118, 195–204. Abstract Glycine synaptic levels are controlled by glycine transporters (GLYTs) catalyzing Na+/Cl−/glycine cotransport. GLYT1 displays a 2 : 1 : 1 stoichiometry and is the main regulator of extracellular concentrations. The neuronal GLYT2, with higher sodium coupling (3 : 1 : 1), supplies to pre-synaptic terminal refill vesicles. In this work, using structural homology modelling molecular dynamics simulations GLYTs, we predict conservation two sites present in template (leucine transporter from Aquifex aeolicus), confirm its use mutagenesis functional analysis. GLYTs Na1 Na2 show differential cation selectivity, as inferred action lithium, non-transport-supporting ion, on Na+-site mutants. lithium responses were unchanged Na1-site mutants, but abolished or inverted mutants site, which binds presence low concentrations therefore, controls responses. Here, report, for first time, that exerts opposite actions isoforms. Glycine transport inhibited whereas GLYT2 stimulated, effect more evident at increased contrast GLYT1, high affinity lithium-binding processes detected GLYT2.