Regulation of Actomyosin Contractility in Non-Muscle Cells

Abstract

Actomyosin contractility in non-muscle cells is involved in numerous essential processes, including maintenance of cell architecture, environmental sensing, migration, trafficking, polarization, and cytokinesis, to name but a few. An extensive network of structural and regulatory proteins is collectively responsible for the generation of actomyosin contractility forces in the appropriate time and location within the cell to facilitate these processes. We recently mined the literature and protein databases to define this network, which we termed the Contractome (J Cell Sci. 2015 Jun 15;128(12):2209-17), with 100 proteins and over 230 interactions. A systems level analysis of the Contractome highlights key regulatory pathways involved in the assembly and activation of diverse actomyosin structures.Regulation of actin and myosin structures at the molecular level can have effects on cell level dynamics. This is exemplified by the evolutionarily conserved F-actin bundling protein plastin (a.k.a. fimbrin), which we show to be essential for polarization and cytokinesis of the C. elegans zygote. PLST-1 decorates all F-actin structures in the zygote cortex. In a mutant that abrogates the bundling activity of PLST-1, myosin foci in the cortex are distinctly smaller than in the wild-type, and while cortical contractions still occur over short distances, there is a lack of coordination in the contractile network over large length scales. This results in a substantial reduction in anterior directed cortical flow, which leads to defects in the establishment of polarity. PLST-1 is also required for cell division, as loss of PLST-1 function results in a significant delay or complete failure in cytokinesis. Thus, interlinking of the cortical network by plastin allows forces to be transmitted at a much longer length scale, facilitating the integration of local contractile events throughout the meshwork into the effective cortical forces necessary for polarity establishment and cell division.