Reviews & Analysis

Understanding how self-renewal and pluripotency — two key characteristics of stem cells — are controlled may allow generation of stem cell lines from somatic tissues, thus avoiding the ethically contentious need to derive them from embryos. A step forward in this understanding was recently taken by two teams, who exploited recombinant retroviruses in gain-and-loss of function experiments to characterize candidate transcription factors with the potential to regulate 'stemness'.

During anaphase, the cysteine protease separase cleaves cohesin and releases sister chromatids. In budding yeast, separase also has a crucial non-proteolytic role in triggering mitotic exit. Separase performs a similar non-catalytic function in frog and mouse oocytes through its physical interaction with cdk1. Vertebrate separase is therefore essential not only for homologue disjunction, but also for bringing about the end of meiosis I.

A new study shows that alveolar macrophages use the cystic fibrosis transmembrane-conductance regulator (CFTR) to maintain lysosomes at low pH and to restrict the growth of ingested bacteria. This may help to explain the persistent infections and chronic inflammation of the lungs that characterize cystic fibrosis.

Cell division in eukaryotes involves a complex self-organization process that drives the transient assembly of dynamic microtubules into a bipolar spindle around the chromosomes to segregate them to the two daughter cells. Spindle shape and size do not depend on the initial spatial organization of the chromatin, but are determined by microtubule motor activities.

Kinesins conventionally act as molecular motor proteins that translocate along microtubules. However, several kinesins also control microtubule polymerization dynamics. New work shows that the yeast kinesin-8 Kip3p has a unique combination of plus-end motor and plus-end depolymerase activities. These activities facilitate the positioning of the mitotic spindle at the cell cortex.

Cool-1 was previously identified as an effector of activated Cdc42 and as a regulator of epidermal growth factor receptor (EGFR) trafficking. Cool-1 has now been shown to be a phosphorylation-dependent activator of Cdc42 that contributes to transformation by Src, thus proving to be an unusually versatile signalling protein.

RING-finger ubiquitin ligases elicit ubiquitination of their substrates, which is balanced by their self-ubiquitination. New insights into regulating the switch between these two modes are illustrated by the role of the adaptor protein Daxx (death domain-associated protein) in regulating the deubiquitinating enzyme HAUSP which, in turn, directs the ligase activity of Mdm2.

The RhoGTPases Rac and Rho are important for orchestrating cytoskeletal dynamics during cell migration and crosstalk to antagonize each others' activities. The discovery of a Rac GTPase activating protein (GAP) that is regulated by Rho and Rho kinase (ROCK) provides a new basis for this crosstalk.

Actin filament branch initiation by the Arp2/3 complex requires that the Arp2 and Arp3 subunits are loaded with ATP. However, whether ATP hydrolysis is required for branch initiation or subsequent debranching is controversial. New analysis of budding yeast Arp2/3 mutants suggests that debranching, not branching, depends on ATP hydrolysis.

Gleevec inhibits the oncogenic BCR–ABL tyrosine kinase in chronic myelogenous leukaemia and thus safely and effectively suppresses this human cancer. Gleevec also inhibits the normal cellular ABL, a downstream effector of the Eph-receptors, which mediate repulsive cell–cell interactions to regulate axon guidance, angiogenesis and epithelial homeostasis. New work shows that Eph-dependent tumour suppression requires ABL and is blocked by Gleevec, thus cautioning against the indiscriminate use of this drug in cancer therapy.

Ubiquitin, best known as a degradation signal, is also a protein-sorting tag on endocytic cargoes and a regulatory switch on endocytic adaptor proteins. Parkin, a ubiquitin ligase whose mutations are associated with Parkinson's disease, has now been shown to control EGF-receptor internalization and Akt signalling by ubiquitination of the endocytic scaffold protein Eps15.

Actin and actin-binding factors have been implicated in nuclear processes such as chromatin remodelling, mRNA processing and export, and transcription. Until now, actin was assumed to function in these processes as a monomer; however, new work suggests that polymerized actin and its effectors may also be important, particularly in transcription.

The general amino acids permease Gap1p provides yeast with sufficient amino acids to maintain protein synthesis. Gap1p is translocated to the plasma membrane when amino acids become limiting, a process that is mediated by a newly identified membrane complex called the GSE complex.

The mode of propagation of the centrosome has suggested the participation of nucleic acid but four decades of inquiry have been inconclusive. A recent study has provided evidence that centrosomes isolated from clam oocytes are associated with specific RNAs, at least one of which seems to be an mRNA.

Precise spatial regulation of mRNA remodelling is crucial for proper gene expression. One way this is accomplished is through activation of the DEAD-box helicase Dbp5 at the cytoplasmic fibrils of the nuclear-pore complex, by the nucleoporin Gle1 and the soluble inositol polyphosphate InsP₆.

Rises in cytoplasmic Ca²⁺ concentration control a diverse array of key cellular functions. One ubiquitous route for raising Ca²⁺ concentration is through store-operated calcium channels in the plasma membrane. However, the molecular basis of store-operated entry has remained a mystery. Now, exciting new research may have identified the molecular composition of a store-operated channel.