Cytokinesis: Robust cell shape regulation

Abstract

Cytokinesis, the final step of cell division, is a great example of robust cell shape regulation. A wide variety of cells ranging from the unicellular Dictyostelium to human cells in tissues proceed through highly similar, stereotypical cell shape changes during cell division. Typically, cells first round up forming a cleavage furrow in the middle, which constricts resulting in the formation of two daughter cells. Tight control of cytokinesis is essential for proper segregation of genetic and cellular materials, and its failure is deleterious to cell viability. Thus, biological systems have developed elaborate mechanisms to ensure high fidelity of cytokinesis, including the existence of multiple biochemical and mechanical pathways regulated through feedback. In this review, we focus on the built-in redundancy of the cytoskeletal machinery that allows cells to divide successfully in a variety of biological and mechanical contexts. Using Dictyostelium cytokinesis as an example, we demonstrate that the crosstalk between biochemical and mechanical signaling through feedback ensures correct assembly and function of the cell division machinery.

Uniaxial loading induces a scalable switch in cortical actomyosin flow polarization and reveals mechanosensitive regulation of cytokinesis

“…Under these conditions, the remodeling of linear cortical structures seems crucial for the re-distribution of contractile cortical material towards the cleavage furrow by longitudinal flow and assembly of a contractile equatorial ring. Taken together, our findings show that Ray Rappaport’s notion that the cytokinesis machinery is ‘overbuilt, inefficient, never-failed, and repaired by simple measures’ [1] – in other words that cytokinesis is a robust process due to redundant regulators – might only be appropriate for unstressed cells, however, apparently redundant factors can become essential under mechanical stress.…”

“…While cells remodel their actomyosin cortex during cell division, they have to simultaneously integrate chemical and mechanical stimuli from the local environment to ensure successful cytokinesis. In order for cytokinesis to be robust yet responsive to extrinsic stimuli, three fundamental control principles have evolved, (a) redundancy [1], (b) mechanosensitivity [2], and (c) positive/negative feedback [3]. Examples for these control principles are (a) partially redundant molecular motors, actin cross-linkers, and membrane trafficking pathways, (b) molecular mechanosensitivity of integral cytokinesis proteins such as non-muscle myosin II, α-actinin, and filamin [4, 5], and (c) RhoA-dependent self-enhancing local assembly and contraction of actomyosin as well as astral microtubule-based suppression of actomyosin contractility [6], which both are required to generate cortical contractile actomyosin flow during cell division.…”

Harnessing the adaptive potential of mechanoresponsive proteins to overwhelm pancreatic cancer dissemination and invasion

“…In the mechanobiome, forces are shared between myosin II and different actin crosslinkers, with myosin II having potentiating or inhibitory effects on certain crosslinkers and vice versa 31,54 . This mechanosensory system constitutes a control system where mechanical inputs can be converted to signaling outputs in a manner analogous to chemical signal transduction 34,55 . Through our work 31 , an important delineation has emerged: the cell has at least two systems of proteins that when depleted, lead to a reduction in cortical viscoelasticity and tension.…”

The past, present and future of Dictyostelium as a model system

“…Dictyostelium has been and still is a leading model for eukaryotic chemotaxis (Devreotes and Horwitz, 2015), and one of the established models for other motility-linked processes, such as cytokinesis (Srivastava et al, 2016), phagocytosis (Bozzaro et al, 2008), macropinocytosis and endo-lysosomal traffic ; . Concerning cell motility, an uninterrupted series of studies in the last 50 years has led to the identification and characterization of the acto-myosin cytoskeleton underlying changes in cell shape and cell motility processes, with many cytoskeletal proteins first identified and/or characterized in Dictyostelium, such as coronin, the actin nucleator SCAR, the 34-kDa actin-crosslinking protein, myosin I and II, and formins (see Bozzaro, 2013 for references).…”