Phosphorylation of NMDA receptors by cyclin B/CDK1 modulates calcium dynamics and mitosis.

Autor: Rosendo-Pineda MJ; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, DF, 04510, Mexico., Vicente JJ; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, 98195, USA., Vivas O; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, 98195, USA., Pacheco J; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, DF, 04510, Mexico., Loza-Huerta A; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, DF, 04510, Mexico., Sampieri A; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, DF, 04510, Mexico., Wordeman L; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, 98195, USA., Moreno C; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, 98195, USA., Vaca L; Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, DF, 04510, Mexico. lvaca@ifc.unam.mx.; Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, 98195, USA. lvaca@ifc.unam.mx.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Nov 12; Vol. 3 (1), pp. 665. Date of Electronic Publication: 2020 Nov 12.
DOI: 10.1038/s42003-020-01393-3
Abstrakt: 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.
Databáze: MEDLINE
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