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Publication : Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter.

First Author  Preobraschenski J Year  2018
Journal  Cell Rep Volume  23
Issue  2 Pages  535-545
PubMed ID  29642010 Mgi Jnum  J:324193
Mgi Id  MGI:7275317 Doi  10.1016/j.celrep.2018.03.055
Citation  Preobraschenski J, et al. (2018) Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter. Cell Rep 23(2):535-545
abstractText  Vesicular glutamate transporters (VGLUTs) fill synaptic vesicles with glutamate and are thus essential for glutamatergic neurotransmission. However, VGLUTs were originally discovered as members of a transporter subfamily specific for inorganic phosphate (Pi). It is still unclear how VGLUTs accommodate glutamate transport coupled to an electrochemical proton gradient DeltamuH(+) with inversely directed Pi transport coupled to the Na(+) gradient and the membrane potential. Using both functional reconstitution and heterologous expression, we show that VGLUT transports glutamate and Pi using a single substrate binding site but different coupling to cation gradients. When facing the cytoplasm, both ions are transported into synaptic vesicles in a DeltamuH(+)-dependent fashion, with glutamate preferred over Pi. When facing the extracellular space, Pi is transported in a Na(+)-coupled manner, with glutamate competing for binding but at lower affinity. We conclude that VGLUTs have dual functions in both vesicle transmitter loading and Pi homeostasis within glutamatergic neurons.
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