Molecular cloning and functional characterization of human vesicular glutamate transporter 3.
Glutamate is the major excitatory neurotransmitter in the mammalian CNS. It is loaded into synaptic vesicles by a proton gradient-dependent uptake system and is released by exocytosis upon stimulation. Recently, two mammalian isoforms of a vesicular glutamate transporter, VGLUT1 and VGLUT2, have been identified, the expression of which enables quantal release of glutamate from glutamatergic neurons. Here, we report a novel isoform of a human vesicular glutamate transporter (hVGLUT3). The predicted amino acid sequence of hVGLUT3 shows 72% identity to both hVGLUT1 and hVGLUT2. hVGLUT3 functions as a vesicular glutamate transporter with similar properties to the other isoforms when it is heterologously expressed in a neuroendocrine cell line. Although mammalian VGLUT1 and VGLUT2 exhibit a complementary expression pattern covering all glutamatergic pathways in the CNS, expression of hVGLUT3 overlaps with them in some brain areas, suggesting molecular diversity that may account for physiological heterogeneity in glutamatergic synapses.
Takamori
Shigeo
S
Department of Neurobiology, Max-Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Malherbe
Pari
P
Broger
Clemens
C
Jahn
Reinhard
R
D000595:Amino Acid Sequence; D026922:Amino Acid Transport Systems, Acidic / Q000737:chemistry* / Q000235:genetics*; D001692:Biological Transport; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D050496:Vesicular Glutamate Transport Proteins
D026922:Amino Acid Transport Systems, Acidic; D018076:DNA, Complementary; D012333:RNA, Messenger; C460879:SLC17A8 protein, human; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid