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

Publication date: 10 April 2018
Source:Cell Reports, Volume 23, Issue 2
Author(s): Julia Preobraschenski, Cyril Cheret, Marcelo Ganzella, Johannes Friedrich Zander, Karin Richter, Stephan Schenck, Reinhard Jahn, Gudrun Ahnert-Hilger
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.

Graphical abstract

Teaser

Preobraschenski et al. show that the vesicular glutamate transporter functions as a bi-directional phosphate transporter that is coupled with different cations in each direction and hence may play a key role in neuronal phosphate homeostasis.


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