Cell-intrinsic and -extrinsic mechanisms promote cell-type-specific cytokinetic diversity

Abstract

Cytokinesis, the physical division of one cell into two, is powered by constriction of an actomyosin contractile ring. It has long been assumed that all animal cells divide by a similar molecular mechanism, but growing evidence suggests that cytokinetic regulation in individual cell types has more variation than previously realized. In the four-cell Caenorhabditis elegans embryo, each blastomere has a distinct cell fate, specified by conserved pathways. Using fast-acting temperature-sensitive mutants and acute drug treatment, we identified cell-type-specific variation in the cytokinetic requirement for a robust forminCYK-1-dependent filamentous-actin (F-actin) cytoskeleton. In one cell (P2), this cytokinetic variation is cell-intrinsically regulated, whereas in another cell (EMS) this variation is cell-extrinsically regulated, dependent on both SrcSRC-1 signaling and direct contact with its neighbor cell, P2. Thus, both cell-intrinsic and -extrinsic mechanisms control cytokinetic variation in individual cell types and can protect against division failure when the contractile ring is weakened.

Cell lineage-dependent chiral actomyosin flows drive cellular rearrangements in early development

“…1(c)). The molecular composition of the cortex may therefore be different in the AB and P/EMS lineage, which is consistent with a recent study showing that both lineages are differentially dependent on the actin nucleator CYK-1/mDia for successful cytokinesis [56]. Together, the combined action of cortex composition and the intracellular distribution of molecular motors may also determine the type of chiral flow behavior (Supplement Fig.…”

Cleavage-furrow formation without F-actin inChlamydomonas

“…This observation has some precedents and parallels. Even within the unikonts, it is clear that F-actin is not essential for furrow ingression in many cases (9, 15, 25, 87, 88; and see Introduction), and this may be the rule, rather than the exception, in non-unikonts. For example, in the ciliate Tetrahymena pyriformis , latrunculin A did not block cell division despite a loss of F-actin and a consequent disruption of actin-dependent processes such as food-vacuole formation (39); in the Diplomonad parasite Giardia lamblia , which has one actin but no myosin(38), furrowing occurred efficiently when actin expression was knocked down with a morpholino (89), although the cells were delayed in abscission; and in the red alga C. merolae , which also has no myosin, cells divide by furrowing even though actin is not expressed under normal growth conditions (90).…”

Developmental Diversity in Cell Division Mechanisms

“…Finally, since cytokinesis is a remodeling of the cell cortex, cell nonautonomous effects such as fate, size, shape, adhesions, and material properties impact the molecular and mechanical requirements for what is superficially a conserved, generic event. A recent publication in eLife from the lab of Julie Canman at Columbia Medical School reports the use of time-lapse microscopy and conditional loss of protein function in vivo, in the context of a developing embryo (Davies et al, 2018). We discuss how their strategic combination of technologies and logic advanced the field and inspired new questions.…”

“…By developing a rapid temperature shift instrument, the ''Therminator,'' to inactivate temperature sensitive version contractile ring components, Canman and colleagues defined when in C. elegans zygote cytokinesis CYK-1 is required: up until about halfway through cytokinetic ring closure (Davies et al, 2014). Now, Davies et al (2018) report the fascinating finding that certain cells of the 4-cell C. elegans embryo, each of which is differentially fated, exhibit reduced sensitivity to reduction of formin's dimerization and processive F-actin elongation functions (see references within Davies et al, 2018). Thus, already at the 4-cell stage, various cell types have adapted their cytokinetic machinery to altered developmental contexts.…”

“…Similarly, higher levels of the actin depolymerizing drug Latrunculin A were necessary to block cytokinesis in the EMS and P2 cells compared to in the AB cells. In contrast, the four blastomeres and the zygote exhibit the same sensitivity to loss of NMM-II activity via upshift of a thermosensitive allele predicted to have defects in F-actin binding and crosslinking (Davies et al, 2014;Davies et al, 2018).…”