Exit from mitosis induced by a calcium transient: the relation to the MPF and InsP3 dynamics

I Baran1

  • 1Biophysics Laboratory, Biotehnos S.A., Bucharest, Romania.

Bio Systems
|January 1, 1994
PubMed

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.

Related Concept Videos

M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...