Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2)

被引:321
作者
Takamori, S
Rhee, JS
Rosenmund, C
Jahn, R
机构
[1] Max Planck Inst Biophys Chem, Dept Neurobiol, D-37077 Gottingen, Germany
[2] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany
关键词
glutamate; GABA; synaptic vesicle; uptake; vesicular transporter; autapse;
D O I
10.1523/JNEUROSCI.21-22-j0002.2001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Glutamate is the major excitatory neurotransmitter in mammalian CNS. In the presynaptic nerve terminal, glutamate is stored in synaptic vesicles and released by exocytosis. Previously, it has been shown that a transport protein originally identified as a brain-specific Na+-dependent inorganic phosphate transporter I (BNPI) functions as vesicular glutamate transporter and thus has been renamed VGLUT1. Recently, a protein highly homologous to VGLUT1, "differentiation-associated BNPI" (DNPI), has been discovered. Northern blot and in situ hybridization analyses indicate that DNPI mRNA is expressed in some brain regions in which VGLUT1 mRNA is not expressed. We now show that DNPI functions as vesicular glutamate transporter with properties very similar to VGLUT1 and propose to rename the protein VGLUT2. VGLUT2 is highly enriched in synaptic vesicles. Furthermore, VGLUT2 resides on a vesicle population that is distinct from vesicles containing the vesicular GABA transporter or VGLUT1, showing that the expression of VGLUT1 and VGLUT2 do not overlap. When VGLUT2 was expressed in BON cells, membrane fractions displayed ATP-dependent, carbonyl cyanide p-trifluoromethoxyphenylhydrazone- sensitive glutamate uptake. Overexpression of VGLUT2 in cultured autaptic GABAergic neurons yielded postsynaptic currents that were insensitive to the GABAA receptor antagonist bicuculline but blocked by the AMPA-receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfonyl-benzo[F] quinoxaline. Thus, expression of VGLUT2 suffices to cause GABAergic neurons to release glutamate in addition to GABA in a manner very similar to that reported previously for VGLUT1.
引用
收藏
页数:6
相关论文
共 21 条
[1]   Molecular cloning of a novel brain-type Na+-dependent inorganic phosphate cotransporter [J].
Aihara, Y ;
Mashima, H ;
Onda, H ;
Hisano, S ;
Kasuya, H ;
Hori, T ;
Yamada, S ;
Tomura, H ;
Yamada, Y ;
Inoue, I ;
Kojima, I ;
Takeda, J .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (06) :2622-2625
[2]   EXCITATORY AND INHIBITORY AUTAPTIC CURRENTS IN ISOLATED HIPPOCAMPAL-NEURONS MAINTAINED IN CELL-CULTURE [J].
BEKKERS, JM ;
STEVENS, CF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7834-7838
[3]  
Bellocchio EE, 1998, J NEUROSCI, V18, P8648
[4]   Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter [J].
Bellocchio, EE ;
Reimer, RJ ;
Fremeau, RT ;
Edwards, RH .
SCIENCE, 2000, 289 (5481) :957-960
[5]   SYNAPTIC VESICLES IMMUNOISOLATED FROM RAT CEREBRAL-CORTEX CONTAIN HIGH-LEVELS OF GLUTAMATE [J].
BURGER, PM ;
MEHL, E ;
CAMERON, PL ;
MAYCOX, PR ;
BAUMERT, M ;
LOTTSPEICH, F ;
DECAMILLI, P ;
JAHN, R .
NEURON, 1989, 3 (06) :715-720
[6]   HIGH-EFFICIENCY TRANSFORMATION OF MAMMALIAN-CELLS BY PLASMID DNA [J].
CHEN, C ;
OKAYAMA, H .
MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (08) :2745-2752
[7]   Rapid, high level protein production using DNA-based semliki forest virus vectors [J].
DiCiommo, DP ;
Bremner, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (29) :18060-18066
[8]  
HELL JW, 1994, CELL BIOL LAB HDB, P567
[9]   Regional expression of a gene encoding a neuron-specific Na+-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain [J].
Hisano, S ;
Hoshi, K ;
Ikeda, Y ;
Maruyama, D ;
Kanemoto, M ;
Ichijo, H ;
Kojima, I ;
Takeda, J ;
Nogami, H .
MOLECULAR BRAIN RESEARCH, 2000, 83 (1-2) :34-43
[10]   CLEAVAGE OF STRUCTURAL PROTEINS DURING ASSEMBLY OF HEAD OF BACTERIOPHAGE-T4 [J].
LAEMMLI, UK .
NATURE, 1970, 227 (5259) :680-+