Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis

We report the discovery of small molecules that target the Rho pathway, which is a central regulator of cytokinesis—the final step in cell division. We have developed a way of targeting a small molecule screen toward a specific pathway, which should be widely applicable to the investigation of any signaling pathway. In a chemical genetic variant of a classical modifier screen, we used RNA interference (RNAi) to sensitize cells and identified small molecules that suppressed or enhanced the RNAi phenotype. We discovered promising candidate molecules, which we named Rhodblock 1–8, and we identified the target of Rhodblock 6 as Rho kinase. Several Rhodblocks inhibited one function of the Rho pathway in cells: the correct localization of phosphorylated myosin light chain during cytokinesis. Rhodblocks differentially perturb Rho pathway proteins in cells and can be used to dissect the mechanism of the Rho pathway during cytokinesis. © 2010 Nature America, Inc. All rights reserved. Rho GTPases are key regulators of cell division and control other processes that involve the cytoskeleton, such as cell migration, contraction and adhesion1. With Rho GTPases at the center of complicated signaling cascades that are only partially understood, different branches of these pathways cooperate to coordinate these processes. Small GTPases regulate their downstrea

Circadian clocks — the fall and rise of physiology

Circadian clocks control the daily life of most light-sensitive organisms — from cyanobacteria to humans. Molecular processes generate cellular rhythmicity, and cellular clocks in animals coordinate rhythms through interaction (known as coupling). This hierarchy of clocks generates a complex, ~24-hour temporal programme that is synchronized with the rotation of the Earth. The circadian system ensures anticipation and adaptation to daily environmental changes, and functions on different levels — from gene expression to behaviour. Circadian research is a remarkable example of interdisciplinarity, unravelling the complex mechanisms that underlie a ubiquitous biological programme. Insights from this research will help to optimize medical diagnostics and therapy, as well as adjust social and biological timing on the individual level.