title: Expression of the vesicular glutamate transporters during development indicates the widespread corelease of multiple neurotransmitters.
abstract: Three closely related proteins transport glutamate into synaptic vesicles for release by exocytosis. Complementary patterns of expression in glutamatergic terminals have been reported for VGLUT1 and VGLUT2. VGLUT3 shows expression by many cells not considered to be glutamatergic. Here we describe the changes in VGLUT expression that occur during development. VGLUT1 expression increases gradually after birth and eventually predominates over the other isoforms in telencephalic regions. Expressed at high levels shortly after birth, VGLUT2 declines with age in multiple regions, in the cerebellum by 14-fold. In contrast, Coexpression of the two isoforms occurs transiently during development as well as permanently in a restricted subset of glutamatergic terminals in the adult. VGLUT3 is transiently expressed at high levels by select neuronal populations, including terminals in the cerebellar nuclei, scattered neurons in the cortex, and progenitor-like cells, implicating exocytotic glutamate release in morphogenesis and development. VGLUT3 also colocalizes extensively during development with the neuronal vesicular monoamine transporter VMAT2, with the vesicular acetylcholine transporter VAChT, and with the vesicular gamma-aminobutyric acid transporter VGAT. Such coexpression occurs particularly at some specific developmental stages and is restricted to certain sets of cells. In skeletal muscle, VGLUT3 localizes to granular organelles in the axon terminal as well as in the muscle sarcoplasm. The results suggest novel mechanisms and roles for regulated transmitter release.
authors.affiliation: Institute of Basic Medical Sciences and the Centre for Molecular Biology and Neuroscience, University of Oslo, N-0317 Oslo, Norway.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Qureshi
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Seal
authors.forename: Amina
authors.initials: A
authors.lastname: Rafiki
authors.forename: Vidar
authors.initials: V
authors.lastname: Gundersen
authors.forename: Linda H
authors.initials: LH
authors.lastname: Bergersen
authors.forename: Robert T
authors.initials: RT
authors.lastname: Fremeau
authors.forename: Robert H
authors.initials: RH
authors.lastname: Edwards
authors.forename: Jon
authors.initials: J
authors.lastname: Storm-Mathisen
authors.forename: Farrukh A
authors.initials: FA
authors.lastname: Chaudhry
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D026922:Amino Acid Transport Systems, Acidic / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020033:Protein Isoforms; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050496:Vesicular Glutamate Transport Proteins; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D027322:Amino Acid Transport System X-AG; D026922:Amino Acid Transport Systems, Acidic; D026901:Membrane Transport Proteins; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; C460879:SLC17A8 protein, human; C493477:Slc17a6 protein, mouse; C493475:Slc17a6 protein, rat; C493465:Slc17a7 protein, mouse; 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; D018698:Glutamic Acid