Substrate recognition and allosteric regulation of synaptic vesicle glutamate transporter VGLUT2.
Fei Li, Jacob Eriksen, Juan A Oses-Prieto, Yessica K Gomez, Hongfei Xu, Surabhi Hareendranath, Poulomi Das, Janet Finer-Moore, Phuong Nguyen, Alisa Bowen and 5 more
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
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Robert M StroudDepartment of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA. stroud@msg.ucsf.edu.ORCID http://orcid.org/0000-0003-2083-5665
Robert H EdwardsDepartments of Neurology and Physiology, UCSF School of Medicine, San Francisco, CA, USA. robert.edwards@ucsf.edu.ORCID http://orcid.org/0000-0002-8650-3260
Funding
The Stanford-SLAC CryoEM Center supplementU24GM129541 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH, HEDMAN, BRITT · 2018 to 2023
$54.8M
Structural Basis of Vesicular Neurotransmitter TransportR01NS089713 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARDS, ROBERT H, STROUD, ROBERT M · 2015 to 2023
$5.8M
Transport of Neurotransmitter Into Synaptic VesiclesR37MH050712 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI EDWARDS, ROBERT H · 2012 to 2020
$3.5M
Computational Studies of Sodium SymportersR01GM089740 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRABE, MICHAEL · 2011 to 2020
$2.8M
Acquisition of an electron microscope for high-resolution single particle cryo-EMS10OD021741 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2016 to 2016
$2.0M
Glutamate Transport into Synaptic VesiclesR01NS129803 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROBERT H EDWARDS · 2023 to 2026
$2.0M
Glacios™ Cryo Transmission Electron Microscope with 200 kV XFEG opticsS10OD026881 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2019 to 2019
$1.8M
Ion permeation, lipid flipping, and membrane remodeling by TMEM16 proteinsR01GM137109 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRABE, MICHAEL · 2021 to 2024
$1.4M
Molecular Basis for Transmembrane Conduction & SignalingR35GM156263 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Robert M Stroud · 2025 to 2026
$1.2M
Linux cluster for near atomic resolution single particle cryo-EMS10OD020054 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, YIFAN · 2015 to 2015
$456k
Structural Basis of Quantal ReleaseK99MH119591 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LI, FEI · 2019 to 2020
The concentration of neurotransmitters inside synaptic vesicles (SVs) underlies the quantal nature of synaptic transmission. Uptake of glutamate, the principal excitatory neurotransmitter, is driven by membrane potential. To prevent nonquantal efflux of glutamate after SV exocytosis, the vesicular glutamate transporters (VGLUTs) are allosterically inhibited by the neutral pH of the synaptic cleft. To elucidate the mechanism, we determined high-resolution structures of rat VGLUT2 with a cyclic analog of glutamate. We propose a mechanism of substrate recognition in which a positively charged cytoplasmic vestibule electrostatically attracts the negatively charged substrate. We also identify modification of VGLUT2 by palmitoylation and find that this promotes retrieval of the transporter after exocytosis. The structure also reveals an extensive network of electrostatic interactions that forms the cytoplasmic gate. Functional analysis of a mutant that disrupts the network shows how this cytoplasmic gate confers the allosteric requirement for lumenal H
Indexed as
Synaptic VesiclesVesicular Glutamate Transport Protein 2Allosteric RegulationAnimalsExocytosisGlutamic AcidModels, MolecularRatsGlutamic AcidSlc17a6 protein, ratVesicular Glutamate Transport Protein 2
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.