The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons.
Before their exocytotic release during stimulation of nerve terminals, nonpeptide neurotransmitters are loaded into synaptic vesicles by specific transporters. Recently, a protein initially identified as brain-specific Na(+)-dependent inorganic phosphate transporter I (BNPI) has been shown to represent a vesicular glutamate transporter (VGLUT1). In this study, we investigated whether a highly homologous "differentiation-associated Na(+)-dependent inorganic phosphate transporter" (DNPI) is involved in glutamatergic transmission. Vesicles isolated from BON cells expressing recombinant DNPI accumulated l-glutamate with bioenergetical and pharmacological characteristics identical to those displayed by VGLUT1 and by brain synaptic vesicles. Moreover, DNPI localized to synaptic vesicles, at synapses exhibiting classical excitatory features. DNPI thus represents a novel vesicular glutamate transporter (VGLUT2). The distributions of each VGLUT transcript in brain were highly complementary, with only a partial regional and cellular overlap. At the protein level, we could only detect either VGLUT1- or VGLUT2-expressing presynaptic boutons. The existence of two VGLUTs thus defines distinct subsets of glutamatergic neurons.
Herzog
E
E
Institut National de la Santé et de la Recherche Médicale U513, Faculté de Médecine, 94010 Créteil Cedex, France.
Bellenchi
G C
GC
Gras
C
C
Bernard
V
V
Ravassard
P
P
Bedet
C
C
Gasnier
B
B
Giros
B
B
El Mestikawy
S
S
D026905:Amino Acid Transport Systems; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D018698:Glutamic Acid / Q000378:metabolism*; D017403:In Situ Hybridization; D026901:Membrane Transport Proteins; D009474:Neurons / Q000145:classification / Q000378:metabolism*; D009928:Organ Specificity; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000378:metabolism; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins
D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D028061:Phosphate Transport Proteins; D012333:RNA, Messenger; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; C118623:Slc32a1 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid