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.
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.
- MeSH
- Gene Expression MeSH
- Rats MeSH
- Humans MeSH
- Brain cytology metabolism MeSH
- Neurons metabolism MeSH
- Excitatory Amino Acid Transporter 5 biosynthesis genetics MeSH
- Protein Isoforms biosynthesis genetics MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Zmeny exprese GluNl podjednotky N-methyl-D-aspartátového receptoru jsou opakovaně nacházeny u schizofrenie. GluNl c2 je jednou z variant teto podjednotky a konkrétně C2 kazeta je důležitým prvkem při kotvení GluNl do plazmatické membrány. V naší práci jsme hodnotili proteinovou expresi GluNl c2 post mortem v levých a pravých hipokampech pacientů se schizofrenií a kontrol. Výsledky ukázaly na interakci laterality s pohlavím, lateralita u mužů byla obrácená oproti ženám. Vztah hladiny exprese s diagnózou jsme neprokázali.
Changed expression of GluN1 subunit of N-methyl-D-aspartate receptor is repeatedly observed in schizophrenia. GluN1 C2 (C2 cassette), variant of this subunit, is important for insertion GluN1 into the plasma membrane. We have assessed protein expression of GluN1 C2 post mortem in left and right hippocampi of patients with schizophrenia and control. The results showed interaction of laterality and sex and the laterality in man was in reverse to laterality in women. Relation between expression levels and schizophrenia diagnosis was not proven.
- Keywords
- GluNlC2 podjednotka NMDA receptoru,
- MeSH
- Alternative Splicing genetics MeSH
- Financing, Organized MeSH
- Hippocampus metabolism physiopathology MeSH
- Humans MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Protein Subunits biosynthesis genetics MeSH
- Protein Isoforms biosynthesis genetics MeSH
- Receptors, N-Methyl-D-Aspartate biosynthesis genetics MeSH
- Schizophrenia drug therapy metabolism MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
There is accumulating evidence that disturbances in N-methyl-D: -aspartate receptor (NMDA-R) functioning are associated with the pathogenesis of schizophrenia. To assess actual changes in the expression of the GluN1 subunit and its isoforms, we measured absolute differences in the levels of mRNA/protein for panGluN1 (eight isoforms altogether) as well as the mRNA individual isoforms in the postmortem left/right hippocampus of patients with schizophrenia in comparison with non-psychiatric subjects. There were no significant differences in the panGluN1 subunit mRNA expression, but the absolute left/right differences were much more pronounced in the patients with schizophrenia. Protein levels of the GluN1 subunit in the left hippocampus in male schizophrenic patients were lower than controls. The expression of the NR1-4b isoform was attenuated in the left, whereas the NR1-2b was reduced in the right hippocampus of schizophrenic patients. Isoforms associated with the efficiency of NMDA-induced gene expression and with phosphorylation occurred more commonly in schizophrenic hippocampi. In summary, our study suggests that NMDA-R hypofunction in schizophrenia might be selectively dependent on the dysregulation of GluN1 subunit expression, which exhibits a somewhat different expression in the left/right hippocampus of psychotic patients.
- MeSH
- Alternative Splicing MeSH
- Humans MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Protein Subunits biosynthesis genetics MeSH
- Protein Isoforms biosynthesis genetics MeSH
- Receptors, N-Methyl-D-Aspartate biosynthesis genetics MeSH
- Schizophrenia metabolism MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
