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

Abstract：

: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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Preobraschenski J,Cheret C,Ganzella M,Zander JF,Richter K,Schenck S,Jahn R,Ahnert-Hilger G

doi

10.1016/j.celrep.2018.03.055

subject

Has Abstract

pub_date

2018-04-10 00:00:00

pages

535-545

issue

2

issn

2211-1247

pii

S2211-1247(18)30400-5

journal_volume

23

pub_type

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