Abstract
Cytokinesis is the last step of cell division that partitions the cellular organelles and cytoplasm of one cell into two. In animal cells, cytokinesis requires Rho-GTPase-dependent assembly of F-actin and myosin II (actomyosin) to form an equatorial contractile ring (CR) that bisects the cell. Despite 50 years of research, the precise mechanisms of CR assembly, tension generation and closure remain elusive. This hypothesis article considers a holistic view of the CR that, in addition to actomyosin, includes another Rho-dependent cytoskeletal sub-network containing the scaffold protein, Anillin, and septin filaments (collectively termed anillo-septin). We synthesize evidence from our prior work in Drosophila S2 cells that actomyosin and anillo-septin form separable networks that are independently anchored to the plasma membrane. This latter realization leads to a simple conceptual model in which CR assembly and closure depend upon the micro-management of the membrane microdomains to which actomyosin and anillo-septin sub-networks are attached. During CR assembly, actomyosin contractility gathers and compresses its underlying membrane microdomain attachment sites. These microdomains resist this compression, which builds tension. During CR closure, membrane microdomains are transferred from the actomyosin sub-network to the anillo-septin sub-network, with which they flow out of the CR as it advances. This relative outflow of membrane microdomains regulates tension, reduces the circumference of the CR and promotes actomyosin disassembly all at the same time. According to this hypothesis, the metazoan CR can be viewed as a membrane microdomain gathering, compressing and sorting machine that intrinsically buffers its own tension through coordination of actomyosin contractility and anillo-septin-membrane relative outflow, all controlled by Rho. Central to this model is the abandonment of the dogmatic view that the plasma membrane is always readily deformable by the underlying cytoskeleton. Rather, the membrane resists compression to build tension. The notion that the CR might generate tension through resistance to compression of its own membrane microdomain attachment sites, can account for numerous otherwise puzzling observations and warrants further investigation using multiple systems and methods.
Highlights
Cytokinesis of animal cells begins during anaphase with the formation of a cleavage furrow at the cell equator, between the separating chromosomes
We further showed that the contractile ring” (CR)-to-MR transition reflects a balance between two opposing mechanisms acting simultaneously on Anillin: one of cortical retention, the other of membraneassociated removal and Figures 2C,D
Because in the resolved structures we never saw actomyosin co-localizing with anillo-septin, this suggests that either the two sub-networks utilize different membrane attachment sites or that they somehow compete for the same membrane microdomains binding them in a mutually exclusive manner
Summary
Cytokinesis of animal cells begins during anaphase with the formation of a cleavage furrow at the cell equator, between the separating chromosomes. Septins bind PIP2 (Zhang et al, 1999; Tanaka-Takiguchi et al, 2009; Mendonça et al, 2019; Soroor et al, 2019) which stimulates septin polymerization (Bertin et al, 2010) and septin filaments are often found in tight association with the plasma membrane, where they can form membrane diffusion barriers (Takizawa et al, 2000; Dobbelaere and Barral, 2004; Caudron and Barral, 2009) and contribute to cortical rigidity (Gilden and Krummel, 2010; Mostowy and Cossart, 2011) In both worm and fly cells, the recruitment of septins to the CR depends on Anillin (Maddox et al, 2005; Hickson and O’Farrell, 2008b). Considering the CR as a dynamic marriage of these two Rhodependent, Anillin-organized sub-networks is what led to the model elaborated below
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