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. 2020 Mar 4;10:26.
doi: 10.1186/s13578-020-00393-4. eCollection 2020.

Research Progress on the Role of Type I Vesicular Glutamate Transporter (VGLUT1) in Nervous System Diseases

Free PMC article

Research Progress on the Role of Type I Vesicular Glutamate Transporter (VGLUT1) in Nervous System Diseases

Xianchao Du et al. Cell Biosci. .
Free PMC article


Glutamate (Glu) is the predominant excitatory neurotransmitter in the central nervous system (CNS). Glutamatergic transmission is critical for controlling neuronal activity. In presynaptic neurons, Glu is stored in synaptic vesicles and released by stimulation. The homeostasis of glutamatergic system is maintained by a set of transporters in the membrane of synaptic vesicles. The family of vesicular Glu transporters in mammals is comprised of three highly homologous proteins: VGLUT1-3. Among them, VGLUT1 accounts for the largest proportion. However, most of the Glu is transported into the synaptic vesicles via the type 1 vesicle Glu transporter (VGLUT1). So, the expression of particular VGLUT1 is largely complementary with limited overlap and so far it is most specific markers for neurons that use Glu as neurotransmitter. Controlling the activity of VGLUT1 could potentially modulate the efficiency of excitatory neuro-transmission and change the filling level of synaptic vesicles. This review summarizes the recent knowledge concerning molecular and functional characteristic of VGLUT1, their development, contribution to a series of central nervous system and peripheral nervous system diseases such as learning and memory disorders, Alzheimer's disease, Parkinson's disease and sensitized nociception or pain pathology et al.

Keywords: CNS; Glutamate; Nervous system disease; PNS; VGLUT1.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.


Fig. 1
Fig. 1
Glutamate metabolism cycle: After release of glutamate from the presynaptic neurons, a small percentage of glutamate is taken up by post-synaptic glutamate receptors and transporters. While the majority of this synaptically-released glutamate diffuses out of the synaptic cleft is taken up by astrocytic EAATs and mGluRs. In astrocytes, glutamate could be converted to glutamine by glutamine synthetase (GS), then glutamine is released to the synaptic cleft to be taken up by presynaptic neurons and used to resynthesize glutamate. The synaptic vesicles (SVs) uptake the resynthesize glutamate by VGLUTs to release back to the synaptic cleft through synaptic vesicles cycle
Fig. 2
Fig. 2
VGLUT1 transport glutamate (Glu) mechanism diagram. VGLUT1 use proton electrochemical gradient generated by vascular ATPase to carry the glutamata anion (Glu) into the interior of synaptic vesicles. The outflow of chloride ions in synaptic vesicles increases the transport efficiency of VGLUT1. Another explanation is that VGLUT1 transports chloride ions out and transfers equal amounts of Glu. In summary, VGLUT1 acts as a transporter through two pathways

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