IPIP27 Coordinates PtdIns(4,5)P Homeostasis for Successful Cytokinesis.

During cytokinesis, an actomyosin contractile ring drives the separation of the two daughter cells. A key molecule in this process is the inositol lipid PtdIns(4,5)P, which recruits numerous factors to the equatorial region for contractile ring assembly. Despite the importance of PtdIns(4,5)P in cytokinesis, the regulation of this lipid in cell division remains poorly understood.

Kinetochore-localized PP1-Sds22 couples chromosome segregation to polar relaxation.

Cell division requires the precise coordination of chromosome segregation and cytokinesis. This coordination is achieved by the recruitment of an actomyosin regulator, Ect2, to overlapping microtubules at the centre of the elongating anaphase spindle. Ect2 then signals to the overlying cortex to promote the assembly and constriction of an actomyosin ring between segregating chromosomes.

Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis.

Drosophila melanogaster Polo and its human orthologue Polo-like kinase 1 fulfill essential roles during cell division. Members of the Polo-like kinase (Plk) family contain an N-terminal kinase domain (KD) and a C-terminal Polo-Box domain (PBD), which mediates protein interactions. How Plks are regulated in cytokinesis is poorly understood.

Opposing actions of septins and Sticky on Anillin promote the transition from contractile to midbody ring.

During cytokinesis, closure of the actomyosin contractile ring (CR) is coupled to the formation of a midbody ring (MR), through poorly understood mechanisms. Using time-lapse microscopy of Drosophila melanogaster S2 cells, we show that the transition from the CR to the MR proceeds via a previously uncharacterized maturation process that requires opposing mechanisms of removal and retention of the scaffold protein Anillin. The septin cytoskeleton acts on the C terminus of Anillin to locally trim away excess membrane from the late CR/nascent MR via internalization, extrusion, and shedding, whereas the citron kinase Sticky acts on the N terminus of Anillin to retain it at the mature MR.

Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression.

Cell division requires the coordination of critical protein kinases and phosphatases. Greatwall (Gwl) kinase activity inactivates PP2A-B55 at mitotic entry to promote the phosphorylation of cyclin B-Cdk1 substrates, but how Gwl is regulated is poorly understood. We found that the subcellular localization of Gwl changed dramatically during the cell cycle in Drosophila.

Anillin acts as a bifunctional linker coordinating midbody ring biogenesis during cytokinesis.

Animal cell cytokinesis proceeds via constriction of an actomyosin-based contractile ring (CR) [1, 2]. Upon reaching a diameter of ~1 μm [3], a midbody ring (MR) forms to stabilize the intercellular bridge until abscission [4-6]. How MR formation is coupled to CR closure and how plasma membrane anchoring is maintained at this key transition is unknown.

Binucleine 2, an isoform-specific inhibitor of Drosophila Aurora B kinase, provides insights into the mechanism of cytokinesis.

Aurora kinases are key regulators of cell division and important targets for cancer therapy. We report that Binucleine 2 is a highly isoform-specific inhibitor of Drosophila Aurora B kinase, and we identify a single residue within the kinase active site that confers specificity for Aurora B. Using Binucleine 2, we show that Aurora B kinase activity is not required during contractile ring ingression, providing insight into the mechanism of cytokinesis.

Anillin: a pivotal organizer of the cytokinetic machinery.

Cytokinesis is a dynamic and plastic process involving the co-ordinated regulation of many components. Accordingly, many proteins, including the putative scaffold protein anillin, localize to the cleavage furrow and are required for cytokinesis, but how they function together is poorly understood. Anillin can bind to numerous other furrow components, including F-actin, septins and myosin II, but its molecular functions are unclear.

Rho-dependent control of anillin behavior during cytokinesis.

Anillin is a conserved protein required for cytokinesis but its molecular function is unclear. Anillin accumulation at the cleavage furrow is Rho guanine nucleotide exchange factor (GEF)(Pbl)-dependent but may also be mediated by known anillin interactions with F-actin and myosin II, which are under RhoGEF(Pbl)-dependent control themselves. Microscopy of Drosophila melanogaster S2 cells reveal here that although myosin II and F-actin do contribute, equatorial anillin localization persists in their absence.

Rho-kinase controls cell shape changes during cytokinesis.

Background: Animal cell cytokinesis is characterized by a sequence of dramatic cortical rearrangements. How these are coordinated and coupled with mitosis is largely unknown. To explore the initiation of cytokinesis, we focused on the earliest cell shape change, cell elongation, which occurs during anaphase B and prior to cytokinetic furrowing.

Rab11-FIP3 and FIP4 interact with Arf6 and the exocyst to control membrane traffic in cytokinesis.

The dual Rab11/Arf binding proteins, family of Rab11-interacting proteins FIP3 and FIP4 function in the delivery of recycling endosomes to the cleavage furrow and are, together with Rab11, essential for completion of abscission, the terminal step of cytokinesis. Here, we report that both FIP3 and FIP4 bind Arf6 in a nucleotide-dependent manner but exhibit differential affinities for Rab11 and Arf6. Both FIP3 and FIP4 can form ternary complexes with Rab11 and Arf6.

Terminal cytokinesis events uncovered after an RNAi screen.

Much of our understanding of animal cell cytokinesis centers on the regulation of the equatorial acto-myosin contractile ring that drives the rapid ingression of a deep cleavage furrow. However, the central part of the mitotic spindle collapses to a dense structure that impedes the furrow and keeps the daughter cells connected via an intercellular bridge. Factors involved in the formation, maintenance, and resolution of this bridge are largely unknown.

Actin cytoskeleton remodeling during early Drosophila furrow formation requires recycling endosomal components Nuclear-fallout and Rab11.

Cytokinesis requires a dramatic remodeling of the cortical cytoskeleton as well as membrane addition. The Drosophila pericentrosomal protein, Nuclear-fallout (Nuf), provides a link between these two processes. In nuf-derived embryos, actin remodeling and membrane recruitment during the initial stages of metaphase and cellular furrow formation are disrupted.

Arfophilins are dual Arf/Rab 11 binding proteins that regulate recycling endosome distribution and are related to Drosophila nuclear fallout.

Arfophilin is an ADP ribosylation factor (Arf) binding protein of unknown function. It is identical to the Rab11 binding protein eferin/Rab11-FIP3, and we show it binds both Arf5 and Rab11. We describe a related protein, arfophilin-2, that interacts with Arf5 in a nucleotide-dependent manner, but not Arf1, 4, or 6 and also binds Rab11.

Cyclin B destruction triggers changes in kinetochore behavior essential for successful anaphase.

Successful mitosis requires that anaphase chromosomes sustain a commitment to move to their assigned spindle poles. This requires stable spindle attachment of anaphase kinetochores. Prior to anaphase, stable spindle attachment depends on tension created by opposing forces on sister kinetochores [1].