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- Title
Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis.
- Authors
Rosendo-Pineda, Margarita Jacaranda; Vicente, Juan Jesus; Vivas, Oscar; Pacheco, Jonathan; Loza-Huerta, Arlet; Sampieri, Alicia; Wordeman, Linda; Moreno, Claudia; Vaca, Luis
- Abstract
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.
- Subjects
PHOSPHORYLATION; CALCIUM; MITOSIS; ANEUPLOIDY; CANCER
- Publication
Communications Biology, 2020, Vol 3, Issue 1, pN.PAG
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-020-01393-3