| Structural highlights
Function
VGLU2_RAT Mediates the uptake of glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. May also play a role in the endocrine glutamatergic system of other tissues such as pineal gland and pancreas. May also mediate the transport of inorganic phosphate.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Synaptic vesicles accumulate neurotransmitters, enabling the quantal release by exocytosis that underlies synaptic transmission. Specific neurotransmitter transporters are responsible for this activity and therefore are essential for brain function. The vesicular glutamate transporters (VGLUTs) concentrate the principal excitatory neurotransmitter glutamate into synaptic vesicles, driven by membrane potential. However, the mechanism by which they do so remains poorly understood owing to a lack of structural information. We report the cryo-electron microscopy structure of rat VGLUT2 at 3.8-angstrom resolution and propose structure-based mechanisms for substrate recognition and allosteric activation by low pH and chloride. A potential permeation pathway for chloride intersects with the glutamate binding site. These results demonstrate how the activity of VGLUTs can be coordinated with large shifts in proton and chloride concentrations during the synaptic vesicle cycle to ensure normal synaptic transmission.
Ion transport and regulation in a synaptic vesicle glutamate transporter.,Li F, Eriksen J, Finer-Moore J, Chang R, Nguyen P, Bowen A, Myasnikov A, Yu Z, Bulkley D, Cheng Y, Edwards RH, Stroud RM Science. 2020 May 22;368(6493):893-897. doi: 10.1126/science.aba9202. PMID:32439795[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fremeau RT Jr, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH. The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron. 2001 Aug 2;31(2):247-60. PMID:11502256
- ↑ Hayashi M, Otsuka M, Morimoto R, Hirota S, Yatsushiro S, Takeda J, Yamamoto A, Moriyama Y. Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems. J Biol Chem. 2001 Nov 16;276(46):43400-6. Epub 2001 Sep 10. PMID:11551935 doi:http://dx.doi.org/10.1074/jbc.M106244200
- ↑ Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S. The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci. 2001 Nov 15;21(22):RC181. PMID:11698619
- ↑ Takamori S, Rhee JS, Rosenmund C, Jahn R. Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci. 2001 Nov 15;21(22):RC182. PMID:11698620
- ↑ Juge N, Yoshida Y, Yatsushiro S, Omote H, Moriyama Y. Vesicular glutamate transporter contains two independent transport machineries. J Biol Chem. 2006 Dec 22;281(51):39499-506. Epub 2006 Oct 17. PMID:17046815 doi:http://dx.doi.org/M607670200
- ↑ Mackenzie B, Illing AC, Morris ME, Varoqui H, Erickson JD. Analysis of a vesicular glutamate transporter (VGLUT2) supports a cell-leakage mode in addition to vesicular packaging. Neurochem Res. 2008 Feb;33(2):238-47. Epub 2007 Dec 13. PMID:18080752 doi:http://dx.doi.org/10.1007/s11064-007-9546-z
- ↑ Li F, Eriksen J, Finer-Moore J, Chang R, Nguyen P, Bowen A, Myasnikov A, Yu Z, Bulkley D, Cheng Y, Edwards RH, Stroud RM. Ion transport and regulation in a synaptic vesicle glutamate transporter. Science. 2020 May 22;368(6493):893-897. doi: 10.1126/science.aba9202. PMID:32439795 doi:http://dx.doi.org/10.1126/science.aba9202
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