Review Articles in 2010

Preserving a functional set of cytoplasmic organelles requires accurate organelle inheritance at cell division. In yeast, the polarized transport of peroxisomes to daughter cells is balanced by retention mechanisms. Some mechanistic principles apply to the inheritance of all organelles, but the inheritance of some organelles is regulated by specific factors.

Despite its role in long-term gene silencing, DNA methylation is more dynamic than originally thought. Active DNA demethylation occurs during specific stages of development and there is growing evidence to suggest that multiple mechanisms for active DNA demethylation exist.

Mitochondrial outer membrane permeabilization is often required for activation of the caspase proteases that cause apoptotic cell death. As a consequence, the integrity of the mitochondrial outer membrane is highly controlled, primarily through interactions between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein family.

Heat shock 70 kDa proteins (HSP70s) are ubiquitous molecular chaperones that function in modulating polypeptide folding, degradation and translocation across membranes, and protein–protein interactions. This functional diversity is driven by their interaction with J proteins — a diverse class of cofactors.

Despite decades of research, the extent to which human progerias resemble accelerated ageing is still unclear and highly debated. Understanding this connection will require the ongoing characterization of genetic pathways that influence the ageing process in model systems and investigations into molecular pathways that define the pathogenesis of human progerias.

Heat shock factors (HSFs) are essential for survival in a stressful environment. HSFs mediate the heat shock response by binding heat shock elements present in heat shock protein (HSP) genes, thereby mediating their transcription. They are also important regulators of development, lifespan and disease.

Recent work has advanced our understanding of the molecular organization of adherens junctions and how cadherin–catenin complexes at their core engage actin, microtubules and the endocytic machinery. This provides insight into how adherens junctions can maintain tissue architecture and facilitate cell movement during tissue morphogenesis.

The nuclear pore complex is the key regulator of transport between the cytoplasm and nucleus. Emerging evidence suggests it also regulates gene expression by influencing the internal architecture of the nucleus and by coordinating the delivery of genetic information to the cytoplasmic protein synthesis machinery.

The endosomal sorting complex required for transport (ESCRT) machinery catalyses membrane budding in the endolysosomal pathway, which differs from other budding events in that it is directed away from the cytosol. Recent studies have elucidated a mechanism whereby ESCRT-I and ESCRT-II stabilize the bud neck and ESCRT-III mediates neck cleavage.

Monoubiquitylation and polyubiquitylation by Lys63-linked chains contribute to three different pathways related to the maintenance of genome integrity that are responsible for the processing of DNA double-strand breaks, the repair of interstrand cross links and the bypass of lesions during DNA replication.

HSP90 is a highly conserved chaperone that facilitates the maturation of a wide range of proteins. Recent studies have provided insight into the regulation of the HSP90 chaperone cycle and revealed numerous processes that HSP90 regulates directly or indirectly.

Recent discoveries have identified several striking parallels between the cellular factors and molecular events that govern mRNA degradation in eukaryotes and bacteria. Nevertheless, some key distinctions remain, the most fundamental of which may be related to the different mechanisms of translation initiation control.

The discovery of molecular signalling machines such as Ras nanoclusters, spatial activity gradients and flexible network circuitries involving transcriptional feedback, are beginning to reveal the design principles of spatiotemporal organization that are crucial for signalling network function and cell fate decisions.

Our increasingly sophisticated understanding of the molecular mechanisms of cell signalling networks in eukaryotes has revealed a remarkably modular organization. Synthetic biologists are exploring how this can be exploited to engineer cells with novel signalling behaviours that are useful in medicine and biotechnology.

Microscopic approaches that image protein mobility and reactivity have been integral in understanding the spatial organization of signalling molecules. Data from imaging studies, combined with computational and theoretical models, have given us great insight into how cells process information to elicit morphological changes.

Signalling networks regulate the biology of cells and organisms in normal and disease states. Large-scale 'precision proteomics' based on mass spectrometry now enables the system-wide characterization of signalling events, including the quantitative changes of thousands of proteins and their post-translational modifications, in response to any perturbation.

Complex organisms rely on a fairly small number of signalling pathways to regulate all of their responses to developmental and environmental cues. Traditionally, it has been assumed that signalling pathways are linear, but, as exemplified by the Wnt and Hippo pathways, they are now known to achieve considerable levels of diversity and selectivity through extensive integration and crosstalk.

Leukocytes use different strategies to migrate through the endothelium of venular walls and in interstitial tissues. These strategies are regulated by soluble and cell-bound signals. Studies have identified many of the cellular and subcellular events that govern transendothelial migration and are beginning to elucidate the nature of leukocyte interstitial motility.

The link between cytoskeletal actin dynamics and correlated gene activities was unclear. However, the discovery that globular actin polymerization liberates myocardin family transcriptional cofactors to induce serum response factor, which modulates the expression of genes encoding effectors of actin dynamics, has helped bridge this gap in our knowledge.

Non-random positioning of chromosomal domains in the nucleus is a common feature of eukaryotic genomes and has been linked to transcriptional activity, DNA repair, recombination and stability. Nuclear pores and other integral membrane protein complexes are key players in the dynamic organization of the genome in the nucleus.