Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis
| العنوان: | Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis |
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| المؤلفون: | Luis Vaca, Arlet Loza-Huerta, Oscar Vivas, Jonathan Pacheco, Claudia M. Moreno, Margarita Jacaranda Rosendo-Pineda, Linda Wordeman, Juan Jesus Vicente, Alicia Sampieri |
| المصدر: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-13 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Mitotic index, Cyclin B, Medicine (miscellaneous), chemistry.chemical_element, Mitosis, Calcium, Receptors, N-Methyl-D-Aspartate, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, mental disorders, CDC2 Protein Kinase, Animals, Humans, Phosphorylation, Rats, Wistar, lcsh:QH301-705.5, Cells, Cultured, Cyclin-dependent kinase 1, biology, Voltage-dependent calcium channel, Chemistry, musculoskeletal, neural, and ocular physiology, Cell cycle, Molecular biophysics, Cell biology, Chromosome segregation, Rats, 030104 developmental biology, HEK293 Cells, lcsh:Biology (General), nervous system, Astrocytes, biology.protein, Interphase, biological phenomena, cell phenomena, and immunity, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, psychological phenomena and processes |
| الوصف: | N-methyl-D-aspartate receptors (NMDAR) are glutamate-gated calcium channels named after their artificial agonist. NMDAR are implicated in cell proliferation under normal and pathophysiological conditions. However, the role of NMDAR during mitosis has not yet been explored in individual cells. We found that neurotransmitter-evoked calcium entry via endogenous NMDAR in cortical astrocytes was transient during mitosis. The same occurred in HEK293 cells transfected with the NR1/NR2A subunits of NMDAR. This transient calcium entry during mitosis was due to phosphorylation of the first intracellular loop of NMDAR (S584 of NR1 and S580 of NR2A) by cyclin B/CDK1. Expression of phosphomimetic mutants resulted in transient calcium influx and enhanced NMDAR inactivation independent of the cell cycle phase. Phosphomimetic mutants increased entry of calcium in interphase and generated several alterations during mitosis: increased mitotic index, increased number of cells with lagging chromosomes and fragmentation of pericentriolar material. In summary, by controlling cytosolic calcium, NMDAR modulate mitosis and probably cell differentiation/proliferation. Our results suggest that phosphorylation of NMDAR by cyclin B/CDK1 during mitosis is required to preserve mitotic fidelity. Altering the modulation of the NMDAR by cyclin B/CDK1 may conduct to aneuploidy and cancer. Rosendo-Pineda et al. discover that N-methyl-D-aspartate receptors (NMDAR) mediate transient calcium entry in mitosis, dependent on phosphorylation of NMDAR by Cyclin B1/CDK1. They also find that phosphorylation-mimicking mutants of NMDAR cause mitotic defects, suggesting that precise control of NMDAR-mediated calcium entry is needed for proper mitosis. |
| اللغة: | English |
| تدمد: | 2399-3642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::892d7b1aab0d475daddb831df359640cTest http://europepmc.org/articles/PMC7665045Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....892d7b1aab0d475daddb831df359640c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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