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Updated: Aug 6, 2026

Applications of Spatio-temporal Mapping and Particle Analysis Techniques to Quantify Intracellular Ca2+ Signaling In Situ
Published on: January 7, 2019
Exit from mitosis induced by a calcium transient: the relation to the MPF and InsP3 dynamics
1Biophysics Laboratory, Biotehnos S.A., Bucharest, Romania.
Abstract:
Cells divide only after passing through a control point in late G1. This passage is followed by the accumulation of the mitotic cyclin which binds to p34cdc2, allowing for the subsequent phosphorylation and dephosphorylation of the latter protein. It is the active MPF, i.e. the phosphorylated mitotic cyclin-p34cdc2 kinase complex that triggers entry into mitosis. MPF becomes increasingly active as the cell forwards to anaphase, when a sudden increase in InsP3 takes place. This in turn induces a large Ca2+ release in cytosol from internal calcium stores and a calcium-dependent positive feedback control on InsP3-induced calcium release enhances the effect on InsP3-mediated Ca2+ transient. Meanwhile, empty calcium stores signal to plasma membrane for a constant calcium influx at high InsP3 levels. The cytosolic calcium excess is assumed to activate the CaMKll holloenzyme which involves the production of the ubiquitination complex necessary for cyclin degradation and MPF inactivation. Accordingly, a mathematical model was proposed by means of an eight-dimensional dynamical system that yields the time dependence of the main cellular quantities in a picture of the mitosis specific events.
Insights
Cell division requires passing a G1 checkpoint, activating maturation-promoting factor (MPF) via cyclin binding and phosphorylation. Calcium signaling then triggers MPF inactivation, enabling cell cycle progression.
Area of Science:
- Cell Biology
- Biochemistry
- Systems Biology
Background:
- Cell cycle progression is regulated by checkpoints, notably the G1 checkpoint controlling entry into mitosis.
- Mitotic cyclin accumulation and its interaction with p34cdc2 form the maturation-promoting factor (MPF) kinase complex, crucial for initiating mitosis.
Purpose of the Study:
- To elucidate the molecular mechanisms regulating MPF activity and its inactivation during the cell cycle.
- To model the dynamic interplay between calcium signaling and MPF regulation during mitosis.
Main Methods:
- Utilized a mathematical model based on an eight-dimensional dynamical system.
- Simulated the time-dependent behavior of key cellular components involved in mitosis.
Main Results:
- Demonstrated that MPF activity increases towards anaphase, coinciding with a surge in inositol trisphosphate (InsP3).
- Showcased InsP3-induced calcium release from internal stores, amplified by positive feedback, and sustained calcium influx.
- Proposed that elevated cytosolic calcium activates CaMKII, leading to cyclin degradation and MPF inactivation.
Conclusions:
- The study presents a comprehensive model for MPF regulation and inactivation through calcium signaling.
- Highlights the critical role of calcium dynamics in ensuring proper cell cycle progression and timely mitosis completion.
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