期刊
CELL REPORTS
卷 23, 期 2, 页码 535-545出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.03.055
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- Deutsche Forschungsgemeinschaft [GZ: AH 67/9, JA 377/7-1, HO 249/44-1]
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 (P-i). It is still unclear how VGLUTs accommodate glutamate transport coupled to an electrochemical proton gradient Delta mu H+ with inversely directed P-i transport coupled to the Na+ gradient and the membrane potential. Using both functional reconstitution and heterologous expression, we show that VGLUT transports glutamate and P-i 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 Delta mu H+-dependent fashion, with glutamate preferred over P-i. When facing the extracellular space, P-i 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 P-i homeostasis within glutamatergic neurons.
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