Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking
| Autor: | Hongying Tan, Weidong Mi, Zhiyi Zuo, Jiangbei Cao |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Excitatory Amino Acid Transporter 3 Biophysics AMPA receptor Biology Biochemistry Hippocampus Article Biochemical cascade chemistry.chemical_compound Mice Internal medicine medicine Animals Receptors AMPA Molecular Biology Tetraethylammonium Kinase musculoskeletal neural and ocular physiology Tetraethylammonium Compounds Cyclic AMP-Dependent Protein Kinases Cell biology Transport protein Protein Transport Endocrinology nervous system chemistry Knockout mouse Phosphorylation |
| Zdroj: | Biochimica et biophysica acta. 1840(6) |
| ISSN: | 0006-3002 |
| Popis: | Background Rapid trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) to the plasma membrane is considered a fundamental biological process for learning and memory. GluR1 is an AMPAR subunit. We have shown that mice with knockout of excitatory amino acid transporter type 3 (EAAT3), a neuronal glutamate transporter, have impaired learning and memory. The mechanisms for this impairment are not known and may be via regulation of AMPAR trafficking. Methods Freshly prepared 300 μm coronal hippocampal slices from wild-type or EAAT3 knockout mice were incubated with or without 25 mM tetraethylammonium for 10 min. The trafficking of GluR1, an AMPAR subunit, to the plasma membrane and its phosphorylation were measured. Results Tetraethylammonium increased the trafficking of GluR1 and EAAT3 to the plasma membrane in the wild-type mouse hippocampal slices but did not cause GluR1 trafficking in the EAAT3 knockout mice. Tetraethylammonium also increased the phosphorylation of GluR1 at S845, a protein kinase A (PKA) site, in the wild-type mice but not in the EAAT3 knockout mice. The PKA antagonist KT5720 attenuated tetraethylammonium-induced GluR1 phosphorylation and trafficking in the wild-type mice. The PKA agonist 6-BNz-cAMP caused GluR1 trafficking to the plasma membrane in the EAAT3 knockout mice. In addition, EAAT3 was co-immunoprecipitated with PKA. Conclusions These results suggest that EAAT3 is upstream of PKA in a pathway to regulate GluR1 trafficking. General significance Our results provide initial evidence for the involvement of EAAT3 in the biochemical cascade of learning and memory. |
| Databáze: | OpenAIRE |
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