Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study
Background: Glutamate, an excitatory neurotransmitter, plays a pivotal role in cellular phenomena in neurons, like synaptic plasticity and excitotoxicity. As the major glutamate receptors, N-methyl-D-aspartate receptors (NMDARs) undergo phosphorylation at Ser1303 on the GluN2B subunit upon glutamate...
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| Format: | Article |
| Language: | English |
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Guilan University of Medical Sciences
2023-10-01
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| Series: | Caspian Journal of Neurological Sciences |
| Subjects: | |
| Online Access: | http://cjns.gums.ac.ir/article-1-668-en.pdf |
| _version_ | 1797336235800264704 |
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| author | Ramya R Prabhu |
| author_facet | Ramya R Prabhu |
| author_sort | Ramya R Prabhu |
| collection | DOAJ |
| description | Background: Glutamate, an excitatory neurotransmitter, plays a pivotal role in cellular phenomena in neurons,
like synaptic plasticity and excitotoxicity. As the major glutamate receptors, N-methyl-D-aspartate receptors
(NMDARs) undergo phosphorylation at Ser1303 on the GluN2B subunit upon glutamate binding. This effect
results from the influx of calcium and subsequent activation of many known kinases that phosphorylate the
receptor. However, the regulation of this phosphorylation at this site and the involved phosphatases have
remained unknown, especially under excitotoxicity conditions induced by glutamate treatment.
Objectives: This study attempts to investigate the regulation of phosphorylation at GluN2B-Ser1303
under excitotoxic conditions and identify the phosphatase responsible.
Materials & Methods: Primary cortical neurons prepared from embryonic rat brains were treated
with glutamate, thereby inducing excitotoxicity in vitro. Then, the phosphorylation status of
GluN2B-Ser1303 was studied using western blots in the presence of various phosphatase inhibitors.
Finally, the interaction of phosphatase with GluN2B was studied using immunostaining and coimmunoprecipitation
analysis.
Results: The results show that under excitotoxic conditions, there is a reduction in the phosphorylation
of GluN2B-Ser1303, and protein phosphatase 1 (PP1) was the phosphatase responsible. PPI was
found to interact with the receptor.
Conclusion: This study reports for the first time the regulation of phosphorylation at GluN2BSer1303
in vitro under excitotoxic conditions, which PP1 mediates. This site could be a potential drug
target for designing novel compounds which could exacerbate excitotoxicity. |
| first_indexed | 2024-03-08T08:51:18Z |
| format | Article |
| id | doaj.art-7135d360af4c406893c66c82990ce9a6 |
| institution | Directory Open Access Journal |
| issn | 2423-4818 |
| language | English |
| last_indexed | 2024-03-08T08:51:18Z |
| publishDate | 2023-10-01 |
| publisher | Guilan University of Medical Sciences |
| record_format | Article |
| series | Caspian Journal of Neurological Sciences |
| spelling | doaj.art-7135d360af4c406893c66c82990ce9a62024-02-01T09:30:55ZengGuilan University of Medical SciencesCaspian Journal of Neurological Sciences2423-48182023-10-0194259267Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro StudyRamya R Prabhu0 Department of Biotechnology, Faculty of Applied Science, Government Arts College, Trivandrum, India Background: Glutamate, an excitatory neurotransmitter, plays a pivotal role in cellular phenomena in neurons, like synaptic plasticity and excitotoxicity. As the major glutamate receptors, N-methyl-D-aspartate receptors (NMDARs) undergo phosphorylation at Ser1303 on the GluN2B subunit upon glutamate binding. This effect results from the influx of calcium and subsequent activation of many known kinases that phosphorylate the receptor. However, the regulation of this phosphorylation at this site and the involved phosphatases have remained unknown, especially under excitotoxicity conditions induced by glutamate treatment. Objectives: This study attempts to investigate the regulation of phosphorylation at GluN2B-Ser1303 under excitotoxic conditions and identify the phosphatase responsible. Materials & Methods: Primary cortical neurons prepared from embryonic rat brains were treated with glutamate, thereby inducing excitotoxicity in vitro. Then, the phosphorylation status of GluN2B-Ser1303 was studied using western blots in the presence of various phosphatase inhibitors. Finally, the interaction of phosphatase with GluN2B was studied using immunostaining and coimmunoprecipitation analysis. Results: The results show that under excitotoxic conditions, there is a reduction in the phosphorylation of GluN2B-Ser1303, and protein phosphatase 1 (PP1) was the phosphatase responsible. PPI was found to interact with the receptor. Conclusion: This study reports for the first time the regulation of phosphorylation at GluN2BSer1303 in vitro under excitotoxic conditions, which PP1 mediates. This site could be a potential drug target for designing novel compounds which could exacerbate excitotoxicity.http://cjns.gums.ac.ir/article-1-668-en.pdfglutamic acidphosphorylationneuronsglun2b-ser1303excitotoxicity |
| spellingShingle | Ramya R Prabhu Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study Caspian Journal of Neurological Sciences glutamic acid phosphorylation neurons glun2b-ser1303 excitotoxicity |
| title | Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study |
| title_full | Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study |
| title_fullStr | Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study |
| title_full_unstemmed | Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study |
| title_short | Phosphorylation Status of GluN2B-Ser1303 Under Glutamate-induced Excitotoxicity in Primary Cortical Neurons: An In Vitro Study |
| title_sort | phosphorylation status of glun2b ser1303 under glutamate induced excitotoxicity in primary cortical neurons an in vitro study |
| topic | glutamic acid phosphorylation neurons glun2b-ser1303 excitotoxicity |
| url | http://cjns.gums.ac.ir/article-1-668-en.pdf |
| work_keys_str_mv | AT ramyarprabhu phosphorylationstatusofglun2bser1303underglutamateinducedexcitotoxicityinprimarycorticalneuronsaninvitrostudy |