RGD Reference Report - The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone.

Authors: Gras, Christelle  Amilhon, Bénédicte  Lepicard, Eve M  Poirel, Odile  Vinatier, Jacqueline  Herbin, Marc  Dumas, Sylvie  Tzavara, Eleni T  Wade, Mark R  Nomikos, George G  Hanoun, Naïma  Saurini, Françoise  Kemel, Marie-Louise  Gasnier, Bruno  Giros, Bruno  El Mestikawy, Salah 
Citation: Gras C, etal., Nat Neurosci. 2008 Mar;11(3):292-300. doi: 10.1038/nn2052. Epub 2008 Feb 17.
RGD ID: 151665721
Pubmed: PMID:18278042   (View Abstract at PubMed)
DOI: DOI:10.1038/nn2052   (Journal Full-text)

Three subtypes of vesicular transporters accumulate glutamate into synaptic vesicles to promote its vesicular release. One of the subtypes, VGLUT3, is expressed in neurons, including cholinergic striatal interneurons, that are known to release other classical transmitters. Here we showed that disruption of the Slc17a8 gene (also known as Vglut3) caused an unexpected hypocholinergic striatal phenotype. Vglut3(-/-) mice were more responsive to cocaine and less prone to haloperidol-induced catalepsy than wild-type littermates, and acetylcholine release was decreased in striatum slices lacking VGLUT3. These phenotypes were associated with a colocalization of VGLUT3 and the vesicular acetylcholine transporter (VAChT) in striatal synaptic vesicles and the loss of a synergistic effect of glutamate on vesicular acetylcholine uptake. We propose that this vesicular synergy between two transmitters is the result of the unbalanced bioenergetics of VAChT, which requires anion co-entry for continuing vesicular filling. Our study reveals a previously unknown effect of glutamate on cholinergic synapses with potential functional and pharmacological implications.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc17a8Ratregulation of acetylcholine uptake involved_inIDA PMID:18278042UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc17a8  (solute carrier family 17 member 8)

Additional Information