The Value of Mechanistic Biophysical Information for Systems-Level Understanding of Complex Biological Processes Such as Cytokinesis

Abstract

This review illustrates the value of quantitative information including concentrations, kinetic constants and equilibrium constants in modeling and simulating complex biological processes. Although much has been learned about some biological systems without these parameter values, they greatly strengthen mechanistic accounts of dynamical systems. The analysis of muscle contraction is a classic example of the value of combining an inventory of the molecules, atomic structures of the molecules, kinetic constants for the reactions, reconstitutions with purified proteins and theoretical modeling to account for the contraction of whole muscles. A similar strategy is now being used to understand the mechanism of cytokinesis using fission yeast as a favorable model system.

Fission yeast myosin Myo2 is down-regulated in actin affinity by light chain phosphorylation

“…Myo2 Is Active Without Phosphorylation and Rng3. It was anticipated that Myo2 folding in the baculovirus/Sf9 insect cell system might require the coexpression of a species-specific chaperone, like certain unconventional myosins (31,32), because animals and fission yeast are separated by 1 billion years of evolution (2). When Myo2 was coexpressed with its native light chains Cdc4 (ELC) and Rlc1 (RLC), it was not necessary to coexpress the native chaperone, Rng3, to obtain soluble Myo2 ( Fig.…”

“…fission yeast | cytokinesis | myosin-II | phosphorylation A nimals, amoebas, and fungi undergo cytokinesis through the formation of a cleavage furrow, which is guided by tension generated by an actomyosin contractile ring. Relatively little is known about the physical interactions and juxtaposition of proteins in the contractile ring in animal cells (1,2). However, pioneering classical and molecular genetics of the haploid fission yeast Schizosaccharomyces pombe have made it a well-established model organism for understanding how contractile rings assemble and undergo constriction.…”

“…However, pioneering classical and molecular genetics of the haploid fission yeast Schizosaccharomyces pombe have made it a well-established model organism for understanding how contractile rings assemble and undergo constriction. Elucidation of the inventory, timing, concentrations, and genetic interactions of cytokinesis proteins in the fission yeast contractile ring has led to computational models that account for many dynamic aspects of the contractile ring (2). To expand upon these models, better knowledge of the biophysical properties of the proteins involved is needed.…”

Actin assembly mechanisms at a glance

“…Nevertheless, much remains to be learned regarding the regulation of actin assembly in stress fibres, focal adhesions or the mammalian contractile ring (Burridge and Guilluy, 2016;, and fundamental outstanding questions include determination of the obligatory factors and pathways for the formation and turnover of these different contractile arrays, the regulation of length and number of individual actin filaments contributing to these structures, as well as the coordination of their assembly and disassembly during contraction or constriction (Livne and Geiger, 2016;Pollard, 2014).…”

Coordinating septum formation and the actomyosin ring during cytokinesis in Schizosaccharomyces pombe

“…Studies on the regulation of cytokinesis in fission yeast have focused mostly on the structural aspects of the ring and how it is assembled (Laporte et al, 2010;Lee et al, 2012;Pollard, 2014). Recently, super-resolution microscopy enabled the spatial mapping of proteins localized to the cytokinetic nodes and to the ring after assembly, showing their proximity to the ring and the membrane (Laplante et al, 2016;McDonald et al, 2017).…”