title: A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons.
abstract: Two proteins previously known as Na(+)-dependent phosphate transporters have been identified recently as vesicular glutamate transporters (VGLUT1 and VGLUT2). Together, VGLUT1 and VGLUT2 are operating at most central glutamatergic synapses. In this study, we characterized a third vesicular glutamate transporter (VGLUT3), highly homologous to VGLUT1 and VGLUT2. Vesicles isolated from endocrine cells expressing recombinant VGLUT3 accumulated l-glutamate with bioenergetic and pharmacological characteristics similar, but not identical, to those displayed by the type-1 and type-2 isoforms. Interestingly, the distribution of VGLUT3 mRNA was restricted to a small number of neurons scattered in the striatum, hippocampus, cerebral cortex, and raphe nuclei, in contrast to VGLUT1 and VGLUT2 transcripts, which are massively expressed in cortical and deep structures of the brain, respectively. At the ultrastructural level, VGLUT3 immunoreactivity was concentrated over synaptic vesicle clusters present in nerve endings forming asymmetrical as well as symmetrical synapses. Finally, VGLUT3-positive neurons of the striatum and raphe nuclei were shown to coexpress acetylcholine and serotonin transporters, respectively. Our study reveals a novel class of glutamatergic nerve terminals and suggests that cholinergic striatal interneurons and serotoninergic neurons from the brainstem may store and release glutamate.
authors.affiliation: Faculté de Médecine, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 513, 94010 Créteil Cedex, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Gras
authors.forename: Etienne
authors.initials: E
authors.lastname: Herzog
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Bellenchi
authors.forename: Veronique
authors.initials: V
authors.lastname: Bernard
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.forename: Michel
authors.initials: M
authors.lastname: Pohl
authors.forename: Bruno
authors.initials: B
authors.lastname: Gasnier
authors.forename: Bruno
authors.initials: B
authors.lastname: Giros
authors.forename: Salah
authors.initials: S
authors.lastname: El Mestikawy
mesh_terms: D000109:Acetylcholine / Q000032:analysis*; D000595:Amino Acid Sequence; D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D018698:Glutamic Acid / Q000494:pharmacology; D007700:Kinetics; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011903:Raphe Nuclei; D051381:Rats; D016415:Sequence Alignment; D012701:Serotonin / Q000032:analysis*; D013572:Synaptic Vesicles / Q000737:chemistry; D014018:Tissue Distribution; D014158:Transcription, Genetic; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C460879:SLC17A8 protein, human; C493475:Slc17a6 protein, rat; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins; D012701:Serotonin; D018698:Glutamic Acid; D000109:Acetylcholine