RGD Reference Report - Protons Regulate Vesicular Glutamate Transporters through an Allosteric Mechanism. - Rat Genome Database

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Protons Regulate Vesicular Glutamate Transporters through an Allosteric Mechanism.

Authors: Eriksen, Jacob  Chang, Roger  McGregor, Matt  Silm, Katlin  Suzuki, Toshiharu  Edwards, Robert H 
Citation: Eriksen J, etal., Neuron. 2016 May 18;90(4):768-80. doi: 10.1016/j.neuron.2016.03.026. Epub 2016 Apr 28.
RGD ID: 152025528
Pubmed: PMID:27133463   (View Abstract at PubMed)
PMCID: PMC4886649   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2016.03.026   (Journal Full-text)

The quantal nature of synaptic transmission requires a mechanism to transport neurotransmitter into synaptic vesicles without promoting non-vesicular efflux across the plasma membrane. Indeed, the vesicular transport of most classical transmitters involves a mechanism of H(+) exchange, which restricts flux to acidic membranes such as synaptic vesicles. However, vesicular transport of the principal excitatory transmitter glutamate depends primarily on membrane potential, which would drive non-vesicular efflux, and the role of protons is unclear. Adapting electrophysiology to record currents associated with the vesicular glutamate transporters (VGLUTs), we characterize a chloride conductance that is gated by lumenal protons and chloride and supports glutamate uptake. Rather than coupling stoichiometrically to glutamate flux, lumenal protons and chloride allosterically activate vesicular glutamate transport. Gating by protons serves to inhibit what would otherwise be substantial non-vesicular glutamate efflux at the plasma membrane, thereby restricting VGLUT activity to synaptic vesicles.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc17a6RatL-glutamate transmembrane transport involved_inIDA PMID:27133463UniProt 

Molecular Function

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc17a6Ratchloride channel activity enablesIDA PMID:27133463UniProt 
Slc17a8Ratchloride channel activity enablesIDA PMID:27133463UniProt 
Slc17a6RatL-glutamate uniporter activity enablesIDA PMID:27133463UniProt 
Slc17a8RatL-glutamate uniporter activity enablesIDA PMID:27133463UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Slc17a6  (solute carrier family 17 member 6)
Slc17a8  (solute carrier family 17 member 8)

Additional Information