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  Dual and direction-selective mechanisms of phosphate transport by the vesicular glutamate transporter.

Preobraschenski, J., Chere, C., Ganzella, M., Zander, J. F., Richter, K., Schenck, S., et al. (2018). Dual and direction-selective mechanisms of phosphate transport by the vesicular glutamate transporter. Cell Reports, 23(2), 535-545. doi:10.1016/j.celrep.2018.03.055.

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Preobraschenski, J.1, Autor           
Chere, C., Autor
Ganzella, M.1, Autor           
Zander, J. F., Autor
Richter, K., Autor
Schenck, S., Autor
Jahn, R.1, Autor           
Ahnert-Hilger, G., Autor
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              

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Schlagwörter: VGLUT, SLC17 family, type I Na+-dependent inorganic phosphate transporter, ATPase, proteoliposomes, hybrid vesicles, anti-VGLUT1 nanobody
 Zusammenfassung: 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 ΔμH+ 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 ΔμH+-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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Sprache(n): eng - English
 Datum: 2018-04-10
 Publikationsstatus: Online veröffentlicht
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 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: DOI: 10.1016/j.celrep.2018.03.055
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Titel: Cell Reports
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: -
Seiten: - Band / Heft: 23 (2) Artikelnummer: - Start- / Endseite: 535 - 545 Identifikator: -