Molecular, Structural, Functional, and Pharmacological Sites for Vesicular Glutamate Transporter Regulation.

TitleMolecular, Structural, Functional, and Pharmacological Sites for Vesicular Glutamate Transporter Regulation.
Publication TypeJournal Article
Year of Publication2020
AuthorsPietrancosta N, Djibo M, Daumas S, Mestikawy SEl, Erickson JD
JournalMol Neurobiol
Volume57
Issue7
Pagination3118-3142
Date Published2020 Jul
ISSN1559-1182
Abstract

Vesicular glutamate transporters (VGLUTs) control quantal size of glutamatergic transmission and have been the center of numerous studies over the past two decades. VGLUTs contain two independent transport modes that facilitate glutamate packaging into synaptic vesicles and phosphate (Pi) ion transport into the synaptic terminal. While a transmembrane proton electrical gradient established by a vacuolar-type ATPase powers vesicular glutamate transport, recent studies indicate that binding sites and flux properties for chloride, potassium, and protons within VGLUTs themselves regulate VGLUT activity as well. These intrinsic ionic binding and flux properties of VGLUTs can therefore be modulated by neurophysiological conditions to affect levels of glutamate available for release from synapses. Despite their extraordinary importance, specific and high-affinity pharmacological compounds that interact with these sites and regulate VGLUT function, distinguish between the various modes of transport, and the different isoforms themselves, are lacking. In this review, we provide an overview of the physiologic sites for VGLUT regulation that could modulate glutamate release in an over-active synapse or in a disease state.

DOI10.1007/s12035-020-01912-7
Alternate JournalMol Neurobiol
PubMed ID32474835
PubMed Central IDPMC7261050
Grant ListRGPIN/04682-2017 / / National Sciences and Engineering Research Council /
R01 NS113955 / NS / NINDS NIH HHS / United States
RGPIN/386431-2012 / / Natural Sciences and Engineering Research Council /
NS113955-01 / NS / NINDS NIH HHS / United States
R21 NS109668 / NS / NINDS NIH HHS / United States
FRQS 30582 / / Fonds de Recherche du Québec - Santé /
ANR-13-SAMA-0005-01 / / Campus France (FR) /
NS109668 / NS / NINDS NIH HHS / United States