Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and Targets

Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways

The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres

INCENP acts as a protein scaffold that integrates the functions of two crucial mitotic kinases, Aurora B and Polo, at centromeres of mitotic chromosomes

The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres

INCENP acts as a protein scaffold that integrates the functions of two crucial mitotic kinases, Aurora B and Polo, at centromeres of mitotic chromosomes

Non-traditional roles of G protein-coupled receptors in basic cell biology

G protein-coupled receptors (GPCR) are key signaling proteins that regulate how cells interact with their environments. Traditional signaling cascades involving GPCRs have been well described and are well established and very important clinical targets. With the development of more recent technologies, hints about the involvement of GPCRs in fundamental cell biological processes are beginning to emerge. In this review, we give a basic introduction to GPCR signaling and highlight some less well described roles of GPCRs, including in cell division and membrane trafficking, which may occur through canonical and non-canonical signaling pathways

Capping protein regulates actin dynamics during cytokinetic midbody maturation

Significance Actin dynamics drive many steps of cell division. Here, we show that the actin capping protein (CP) is unexpectedly involved in midbody maturation, a poorly understood phase of the cell cycle where cells remodel their intercellular bridges to prepare for separation. The loss of CP results in excessive filamentous actin throughout the cell cycle, but only postfurrowing cytokinesis is inhibited. We propose that optimal actin filament function is achieved by a balance between CP-dependent filament capping and formin-driven polymerization. This raises the intriguing possibility that cells utilize specific types of actin filament networks to progress through division. This finding has profound implications on understanding actin-dependent processes such as cell division, migration, adhesion, and morphogenesis.</jats:p

Lipid Cell Biology:A Focus on Lipids in Cell Division

Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids. </jats:p