Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception
The <i>N</i>-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13196 |
| _version_ | 1797582450609618944 |
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| author | Terry A. McNearney Karin N. Westlund |
| author_facet | Terry A. McNearney Karin N. Westlund |
| author_sort | Terry A. McNearney |
| collection | DOAJ |
| description | The <i>N</i>-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many neuronal and non-neuronal cell functions, including plasticity, survival, and differentiation. Physiologic levels of glutamate agonists and NMDA receptor activation are required for normal neuronal functions such as neuronal development, learning, and memory. When glutamate receptor agonists are present in excess, binding to NMDA receptors produces neuronal/CNS/PNS long-term potentiation, conditions of acute pain, ongoing severe intractable pain, and potential excitotoxicity and pathology. The GluNR1 subunit (116 kD) is necessary as the anchor component directing ion channel heterodimer formation, cellular trafficking, and the nuclear localization that directs functionally specific heterodimer formation, cellular trafficking, and nuclear functions. Emerging studies report the relevance of GluN1 subunit composition and specifically that nuclear GluN1 has major physiologic potential in tissue and/or subnuclear functioning assignments. The shift of the GluN1 subunit from a surface cell membrane to nuclear localization assigns the GluN1 promoter immediate early gene behavior with access to nuclear and potentially nucleolar functions. The present narrative review addresses the nuclear translocation of GluN1, focusing particularly on examples of the role of GluN1 in nociceptive processes. |
| first_indexed | 2024-03-10T23:21:23Z |
| format | Article |
| id | doaj.art-5bca35e509914ff9a923809d93ce35af |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:23Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5bca35e509914ff9a923809d93ce35af2023-11-19T08:13:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171319610.3390/ijms241713196Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/NociceptionTerry A. McNearney0Karin N. Westlund1Department of Neuroscience and Cell Biology, University of Texas Medical Branch Galveston, Galveston, TX 77555-1043, USADepartment of Anesthesiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131-0001, USAThe <i>N</i>-methyl-D-aspartate (NMDA) glutamate receptors function as plasma membrane ionic channels and take part in very tightly controlled cellular processes activating neurogenic and inflammatory pathways. In particular, the NR1 subunit (new terminology: GluN1) is required for many neuronal and non-neuronal cell functions, including plasticity, survival, and differentiation. Physiologic levels of glutamate agonists and NMDA receptor activation are required for normal neuronal functions such as neuronal development, learning, and memory. When glutamate receptor agonists are present in excess, binding to NMDA receptors produces neuronal/CNS/PNS long-term potentiation, conditions of acute pain, ongoing severe intractable pain, and potential excitotoxicity and pathology. The GluNR1 subunit (116 kD) is necessary as the anchor component directing ion channel heterodimer formation, cellular trafficking, and the nuclear localization that directs functionally specific heterodimer formation, cellular trafficking, and nuclear functions. Emerging studies report the relevance of GluN1 subunit composition and specifically that nuclear GluN1 has major physiologic potential in tissue and/or subnuclear functioning assignments. The shift of the GluN1 subunit from a surface cell membrane to nuclear localization assigns the GluN1 promoter immediate early gene behavior with access to nuclear and potentially nucleolar functions. The present narrative review addresses the nuclear translocation of GluN1, focusing particularly on examples of the role of GluN1 in nociceptive processes.https://www.mdpi.com/1422-0067/24/17/13196painnuclear translocationnucleusnucleolusepigeneticsmembrane trafficking |
| spellingShingle | Terry A. McNearney Karin N. Westlund Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception International Journal of Molecular Sciences pain nuclear translocation nucleus nucleolus epigenetics membrane trafficking |
| title | Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception |
| title_full | Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception |
| title_fullStr | Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception |
| title_full_unstemmed | Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception |
| title_short | Pluripotential GluN1 (NMDA NR1): Functional Significance in Cellular Nuclei in Pain/Nociception |
| title_sort | pluripotential glun1 nmda nr1 functional significance in cellular nuclei in pain nociception |
| topic | pain nuclear translocation nucleus nucleolus epigenetics membrane trafficking |
| url | https://www.mdpi.com/1422-0067/24/17/13196 |
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