Recent advances in cytokinesis: understanding the molecular underpinnings

Abstract

During cytokinesis, the cell employs various molecular machineries to separate into two daughters. Many signaling pathways are required to ensure temporal and spatial coordination of the molecular and mechanical events. Cells can also coordinate division with neighboring cells to maintain tissue integrity and flexibility. In this review, we focus on recent advances in the understanding of the molecular underpinnings of cytokinesis.

Keywords: ESCRTIII; FtsZ; NoCut; cytokinesis; myosin.

Figure 1.. Cytokinesis from spindle maturation to abscission.

( A) In Caenorhabditis elegans, centralspindlin non-motor subunit CYK-4 binds to the motor subunit MKLP1, activating MKLP1’s antiparallel microtubule bundling activity. Centralspindlin and C. elegans orthologues of human PRC1 interact to resist cortical dynein pulling forces and prevent midzone rupture. ( B) During actomyosin contraction, DIAPH3 in HeLa cells facilitates de novo synthesis of β-actin to ensure furrow ingression. Formin Cdc12 inhibition by mechanoregulation in fission yeast facilitates contractile ring assembly. On the other hand, MICAL1 oxidation of actin in human and Drosophila cells leads to depolymerization of F-actin filaments at the intercellular bridge. Actin capping protein in HeLa cells antagonizes actin polymerization to facilitate progression to abscission. ( C) In HeLa cells, ATPase Vps4 facilitates endosomal sorting complex required for transport III (ESCRTIII)’s turnover, contributing to ESCRTIII filament assembly at the midbody. ESCRTIII also helps in reforming the nuclear envelope during telophase and cytokinesis.

Figure 2.. Resolution of chromatin bridges.

( A) A trailing dicentric chromatid in Saccharomyces cerevisiae is cleaved during cytokinesis. ( B) A chromatin bridge caused by decondensed or catenated chromatin is resolved by the Aurora B kinase-dependent NoCut pathway. In Caenorhabditis elegans, Aurora B facilitates nuclease LEM-3 recruitment to the midbody to help resolve chromatin bridges. In human cells, Clks phosphorylate Aurora B kinase to activate the NoCut checkpoint. Specifically, in HeLa cells, Aurora B phosphorylation of charged multi-vesicular body protein 4C (CHMP4C) interferes with its membrane remodeling activity. Borealin also inhibits CHMP4C association with the membrane. ( C) In human cells, Chk1 activates Src to form actin patches at the base of chromatin bridges, and Chk1 and Src work cooperatively with Aurora kinase B to delay abscission. In Drosophila neuronal stem cells, myosin II efflux from the ring to the poles facilitates extra cell elongation to allow for the clearance of trailing chromatids. Moreover, in Drosophila larval neuroblasts, Aurora B kinase helps inclusion of the trailing chromatid into the reforming nuclei.

Figure 3.. Intercellular junctions guide contractile machinery assembly and division plane specification in multicellular scenarios.

( A) In the Drosophila notum epithelium, E-cadherin dilution caused by elongation of ingressing adherens junctions induces the accumulation of myosin II at adherens junctions between neighboring cells. ( B) In the Drosophila pupal notum epithelium, tricellular junctions orient the mitotic spindle via Mud, and the resulting tricellular junction bipolarity facilitates cell mechanical strain-induced polarization, guiding the axis of division.