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. |