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Review
. 2021 Sep 15;11(9):4050-4069.
eCollection 2021.

The regulation of actin dynamics during cell division and malignancy

Paulius Gibieža  1 , Vilma Petrikaitė  1
Affiliations
Review

The regulation of actin dynamics during cell division and malignancy

Paulius Gibieža et al. Am J Cancer Res. .

Abstract

Actin is the most abundant protein in almost all the eukaryotic cells. Actin amino acid sequences are highly conserved and have not changed a lot during the progress of evolution, varying by no more than 20% in the completely different species, such as humans and algae. The network of actin filaments plays a crucial role in regulating cells' cytoskeleton that needs to undergo dynamic tuning and structural changes in order for various functional processes, such as cell motility, migration, adhesion, polarity establishment, cell growth and cell division, to take place in live cells. Owing to its fundamental role in the cell, actin is a prominent regulator of cell division, a process, whose success directly depends on morphological changes of actin cytoskeleton and correct segregation of duplicated chromosomes. Disorganization of actin framework during the last stage of cell division, known as cytokinesis, can lead to multinucleation and formation of polyploidy in post-mitotic cells, eventually developing into cancer. In this review, we will cover the principles of actin regulation during cell division and discuss how the control of actin dynamics is altered during the state of malignancy.

Keywords: Actin; abscission; cancer; cleavage furrow; contractile ring; cytokinesis; mitosis; myosin.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Actin polymerization and steady state treadmilling. The G-actin monomers attach to the continually growing barbed (+) end of the filament in a more stable ATP-state to form F-actin strands, which in cells function to support structural integrity during cell division and migration. Upon ATP-hydrolysis-driven F-actin depolymerization, ADP monomers begin to dissociate from the pointed (-) end of the filament at a faster rate than the ATP monomers are bound. This process of steady-state actin polymerization and depolymerization is known as treadmilling. The dynamic regulation of actin elongation is accelerated/decelerated via an action of profilin and ADF/cofilin.
Figure 2
Figure 2
The regulation of actin dynamics during different phases of mitosis. The scheme shows different phases of the cell cycle, depicting the intracellular processes that take place during mitotic (M) phase, and placing a special emphasis on signalling cascades that regulate actin cytoskeleton during the cell cycle progression. During prophase chromosomes condense, spindle fibers emerge from the centrosomes, nuclear envelope breaks down, and centrosomes move towards the opposite poles of the cell. Then, in prometaphase, kinetochores arise at the centrosomes and mitotic spindle microtubules attach to the kinetochores. Next, during metaphase, chromosomes line up at the metaphase plate, while each sister chromatid gets attached to a spindle fiber, outgrowing from the opposite poles. During anaphase, centromere split in two and sister chromatids are pulled towards the opposite poles, while spindle fibers start to elongate the cell. This is followed by telophase, where chromosomes at the opposite poles begin to decondense, and nuclear envelope, surrounding each set of chromosomes, starts to reform. Then, spindle fibers continue to push poles to the opposite directions. Finally, a cleavage furrow, which separates newly formed daughter cells, is formed. The scheme on a right depicts functional relation of proteins, participating in a control of actin dynamics during the M-phase of the cell cycle.
Figure 3
Figure 3
Organization of cellular cytoskeleton during furrow ingression. The picture illustrates the mitotic cleavage furrow formation during anaphase, formation of actomyosin contractile ring in telophase, and final abscission of the ICB during late cytokinesis. In the beginning of anaphase, sister chromatids start to separate upon central spindlin complex entering the spindle midzone. Then, the signalling cascade, which controls reorganization and spatio-temporal dynamics of actin, microtubule, and myosin-II, is activated. This recruits Rho-GEF Ect-2, which activates RhoA and initiates the cleavage furrow formation. In telophase, actomyosin contractile ring and microtubule complex is generated, which produces intracellular forces and tension, required to narrow the furrowing cell at the equatorial actin cortex. In late cytokinetic event, the actin filaments are cleared from the narrowed ICB, where final abscission, mediated by ESCRT-III complex, takes place. Finally, this results in a physical separation of the newly formed daughter cells.
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