Human brain neurons express a novel splice variant of excitatory amino acid transporter 5 (hEAAT5v). Issue 17 (3rd April 2020)

• Record Type: Journal Article
• Authors: Lee, Aven; Balcar, Vladimir J.; McCombe, Pamela; Pow, David V.
• Is Part Of: Journal of comparative neurology. Volume 528:Issue 17(2020)
• Page Start: 3134
• Page End: 3142
• Publication Date: 2020-04-03
• Subjects: AB_2813784 -- alternate splicing -- brain -- EAAT5 -- glutamate -- RRID:AB_2813844 -- transporter; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24907
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: Excitatory amino acid transporter 5 (EAAT5) is a protein that is known to be alternately spliced and to be abundantly expressed in the retina by populations of neurons including photoreceptors and bipolar cells. EAAT5 acts as a slow glutamate transporter and also as glutamate‐gated chloride channel, the chloride conductance being large enough for EAAT5 to serve functionally as an "inhibitory" glutamate receptor. However, there has been a long‐standing view that the classically spliced form of EAAT5 is not abundant or widespread in the brain and so it has not been extensively investigated in the literature. We recently identified a human‐specific splicing form of EAAT5 that was not expressed by rodents but was shown to be a functional glutamate transporter. We have examined the expression of this form of EAAT5, hEAAT5v at the mRNA, and protein level in human brain, and show that populations of human cortical pyramidal neurons and cerebellar Purkinje cells show significant expression of hEAAT5v. Accordingly, we infer that EAAT5 may well be a player in modulating neuronal function in the human brain and propose that its localization in both glutamatergic and GABAergic neurons could be compatible with a role in influencing intracellular chloride and thereby neuronal parameters such as membrane potential rather than acting as a presynaptic glutamate transporter. Abstract : Alternately spliced human EAAT5 (hEAAT5v) which contains an additional intron after exon 7 of normally spliced human EAAT5 (7‐int) was cloned from human brain. Immunocytochemistry reveals expression of this protein in apical (A) and basal (B) dendrites and axons (Ax) of human cortical pyramidal neurons. The protein is also expressed by GABAergic neurons including Purkinje cells. It plausibly functions as a glutamate‐gated chloride conductance rather than as a glutamate transporter.