Dual and Direction-Selective Mechanisms of Phosphate Transport by the Vesicular Glutamate Transporter.
Cell Rep
; 23(2): 535-545, 2018 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-29642010
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.
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MEDLINE
Assunto principal:
Fosfatos
/
Proteína Vesicular 1 de Transporte de Glutamato
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article