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Publication : Vesicular glutamate transporters use flexible anion and cation binding sites for efficient accumulation of neurotransmitter.

First Author  Preobraschenski J Year  2014
Journal  Neuron Volume  84
Issue  6 Pages  1287-301
PubMed ID  25433636 Mgi Jnum  J:324087
Mgi Id  MGI:6838939 Doi  10.1016/j.neuron.2014.11.008
Citation  Preobraschenski J, et al. (2014) Vesicular glutamate transporters use flexible anion and cation binding sites for efficient accumulation of neurotransmitter. Neuron 84(6):1287-301
abstractText  Vesicular glutamate transporters (VGLUTs) accumulate the neurotransmitter glutamate in synaptic vesicles. Transport depends on a V-ATPase-dependent electrochemical proton gradient (DeltamuH+) and requires chloride ions, but how chloride acts and how ionic and charge balance is maintained during transport is controversial. Using a reconstitution approach, we used an exogenous proton pump to drive VGLUT-mediated transport either in liposomes containing purified VGLUT1 or in synaptic vesicles fused with proton-pump-containing liposomes. Our data show that chloride stimulation can be induced at both sides of the membrane. Moreover, chloride competes with glutamate at high concentrations. In addition, VGLUT1 possesses a cation binding site capable of binding H+ or K+ ions, allowing for proton antiport or K+ / H+ exchange. We conclude that VGLUTs contain two anion binding sites and one cation binding site, allowing the transporter to adjust to the changing ionic conditions during vesicle filling without being dependent on other transporters or channels.
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