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Defective SLC17A8 causes autosomal dominant deafness 25 (DFNA25)

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-5619076

PubChem

R-HSA-5619076

Description

There are two classes of glutamate transporters; the excitatory amino acid transporters (EAATs) which depend on an electrochemical gradient of Na+ ions and vesicular glutamate transporters (VGLUTs) which are proton-dependent. Together, these transporters uptake and release glutamate to mediate this neurotransmitter's excitatory signal and are part of the glutamate-glutamine cycle. Three members of the SLC17A gene family (7, 6 and 8) encode VGLUTs 1-3 respectively. This uptake is thought to be coupled to the proton electrochemical gradient generated by the vacuolar type H+-ATPase. They are all expressed in the CNS in neuron-rich areas but SLC17A8 (VGLUT3) is also expressed on astrocytes and in the liver and kidney. Defects in SLC17A8 can cause autosomal dominant deafness 25 (DFNA25; MIM:605583), a form of non-syndromic sensorineural hearing loss. The cochlea expresses SLC17A8 and in mice which lack this transporter are congenitally deaf. Hearing loss is due to the lack of glutamate release by inner hair cells therefore a loss of synaptic transmission at the IHC-afferent nerve synapse. Successful restoration of hearing by gene replacement in mice could be a significant advance toward gene therapy of human deafness (Ruel et al. 2008, Akil et al. 2012).

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying 1 entry
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
Q8NDX2	Vesicular glutamate transporter 3	SLC17A8 VGLUT3	view

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