TY - JOUR AU - Borghans, Bart AU - Dmitrieva, Natalia AU - Nikiforov, Aleksandr AU - Fahlke, Christoph TI - Vesicular and plasma membrane glutamate transporters JO - Frontiers in biophysics VL - 3 SN - 2813-7183 CY - Lausanne PB - Frontiers Media SA M1 - FZJ-2025-05016 SP - 1693508 PY - 2025 N1 - The author(s) declare that financial support was received for theresearch and/or publication of this article. This work was supportedby the Deutsche Forschungsgemeinschaft (DFG, German ResearchFoundation) to CF (FA 301/13-1) as part of the Research Unit FOR2795 (Synapses under stress). AB - Glutamate is the major excitatory neurotransmitter in the mammalian centralnervous system. After exocytotic release from presynaptic nerve terminals,glutamate diffuses across the synaptic cleft and opens postsynaptic ionotropicglutamate receptors, thus depolarizing the postsynaptic neuron. Synaptic activityis terminated by rapid and efficient uptake into surrounding neurons and glialcells. The function of a glutamatergic synapse thus critically depends on twodistinct transport systems: vesicular and plasma membrane glutamatetransporters. Vesicular glutamate transporters (VGLUTs) accumulate glutamatein synaptic vesicles and determine the amount of released glutamate. Plasmamembrane glutamate transporters (excitatory amino acid transporters, EAATs)clear the synaptic cleft from glutamate, setting the time resolution and energydemand of glutamatergic synaptic signaling. Both classes of glutamatetransporters are not only secondary-active transporters, but also function aschloride channels, with different roles in chloride and glutamate homeostasis.Despite similar transport functions, VGLUTs and EAATs are structurally diverseand employ different molecular mechanisms to overcome the same chemicalchallenges. We here review recent progress in understanding the molecular andcellular biophysics of vesicular glutamate transporters and compare theirproperties with plasma membrane glutamate transporters. LB - PUB:(DE-HGF)16 DO - DOI:10.3389/frbis.2025.1693508 UR - https://juser.fz-juelich.de/record/1048917 ER -