Molecular and functional analysis of a novel neuronal vesicular glutamate transporter.
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Packaging and storage of glutamate into glutamatergic neuronal vesicles requires ATP-dependent vesicular glutamate uptake systems, which utilize the electrochemical proton gradient as a driving force. VGLUT1, the first identified vesicular glutamate transporter, is only expressed in a subset of glutamatergic neurons. We report here the molecular cloning and functional characterization of a novel glutamate transporter, VGLUT2, from mouse brain. VGLUT2 has all major functional characteristics of a synaptic vesicle glutamate transporter, including ATP dependence, chloride stimulation, substrate specificity, and substrate affinity. It has 75 and 79% amino acid identity with human and rat VGLUT1, respectively. However, expression patterns of VGLUT2 in brain are different from that of VGLUT1. In addition, VGLUT2 activity is dependent on both membrane potential and pH gradient of the electrochemical proton gradient, whereas VGLUT1 is primarily dependent on only membrane potential. The presence of VGLUT2 in brain regions lacking VGLUT1 suggests that the two isoforms together play an important role in vesicular glutamate transport in glutamatergic neurons.
Bai
L
L
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona 85724, USA. lqbai@yahoo.com
Xu
H
H
Collins
J F
JF
Ghishan
F K
FK
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017403:In Situ Hybridization; D026901:Membrane Transport Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D020033:Protein Isoforms; D051381:Rats; D014018:Tissue Distribution; D014162:Transfection; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; C493476:SLC17A6 protein, human; C493477:Slc17a6 protein, mouse; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid