Reviews & Analysis

Changes in nuclear architecture are a hallmark of ageing in yeast and mammals. These changes seem to be driven by DNA damage, which results in age-related alterations in gene expression, and may be a conserved cause of ageing.

Various stress signals can induce a state of irreversible cell-cycle arrest that is known as cellular senescence. Understanding the causes of cellular senescence has provided insight into some of its consequences: it is important for suppressing cancer and possibly contributes to ageing.

Evidence from rodent and human experimental studies supports the view that a decline in the regenerative function of stem cells with age contributes to mammalian ageing and, possibly, several age-associated diseases. However, a few crucial questions remain to be resolved.

The combination of affinity purification and mass spectrometry (AP–MS) has recently been applied to the detailed characterization of protein complexes and large protein-interaction networks. Emerging AP–MS approaches promise a better understanding of protein-complex stoichiometry, structural organization and the dynamics of protein-complex composition.

Classically, endocytosis involves the formation of clathrin-coated carriers that bud from the plasma membrane by dynamin-dependent mechanisms. Recently, several clathrin-independent endocytic pathways have been identified, which represent the main pathway of entry into cells for a diverse array of cargoes, including receptors, lipids and pathogens.

Many signalling pathways have been shown to control cell shape and cell surface mechanics. Recent insights from diverse disciplines point to adhesion and cortical tension as regulators of cell shape and provide insights into how cell shape controls tissue geometry.

Far from being a static organelle at the end of the endocytic pathway, the lysosome is capable of dynamically fusing with many organelles as well as the plasma membrane. The lysosome provides hydrolytic enzymes for the degradation of macromolecules, has secretory functions and is important for plasma membrane repair.

Intense research has led to the discovery and characterization of a novel signalling network, the Hippo pathway, which is involved in growth control inDrosophila melanogaster. The importance of this pathway is emphasized by its evolutionary conservation and by increasing evidence that its deregulation occurs in human tumours.

Considerable progress has been made in understanding the mechanisms that control cell division in plants. However, little is known about how the cell cycle responds to environmental and developmental stimuli and how the cell cycle is turned on and off.

Although it is now accepted that the infectious agent that causes transmissible spongiform encephalopathies is PrP^Sc, recent insights into the existence of prion strains pose a fascinating challenge to prion research. What is the nature of prion strains? And how can they be discriminated?

Nucleoli are the sites of ribosome-subunit biogenesis, but recent large-scale proteomics analyses and other studies have revealed further cellular functions, including cell-cycle control, stress responses and coordination of the processing and maturation of other classes of ribonucleoprotein in addition to the ribosomal class.

Protein kinases must recognize their correct substrates in a massive background of other potentially phosphorylatable sites. A multitude of mechanisms have evolved to regulate specificity. Individually they are imperfect, but together they coordinate protein phosphorylation with exquisite precision.

Intermediate filaments (IFs) are thought to function as absorbers of mechanical stress and form cytoskeletal networks that serve to support cell shape. The analysis of disease-causing mutations in IF proteins has revealed that IFs also have important roles in cell-type-specific physiological functions.

Owing to the toxic potential of unfolded proteins, their accumulation in the endoplasmic reticulum activates a cellular stress response. This unfolded protein response remodels the secretory pathway to accommodate the load of unfolded proteins or, if the burden is insurmountable, promotes cell death to protect the organism.

Drosophila melanogasterhaemocytes operate as the first line of defence against invading microorganisms during larval and adult life. However, in the developing embryo, haemocytes undergo complex migrations and carry out several non-immune functions that are crucial for successful development.

Recent large-scale functional genomics and proteomics analyses have revealed novel molecules that are involved in regulating centrosome function and biogenesis. Other studies indicate that certain molecules that inhibit the re-replication of DNA might also inhibit centriole reduplication, thereby linking chromosome and centrosome cycles.

Many RNA-binding proteins have a modular structure and are composed of multiple repeats of a few small RNA-binding domains. By arranging the domains in various ways, these proteins can carry out their diverse biological roles in an RNA-specific manner.

Common regulatory enzymes affect the function of the class O of forkhead box transcription factors (FoxOs) and p53 in an opposite manner. Recent findings indicate that this shared yet opposing regulatory network between FoxOs and p53 may underlie a 'trade-off' between disease and lifespan.

Understanding the mechanisms of plant development requires the ability to monitor the spatial and temporal control of gene and protein activity as well as cell behaviours in real timein vivo. The dynamic properties of plant processes can now be captured through the simultaneous use of live imaging and transient perturbation technologies.

During the cell cycle, organelles such as the endoplasmic reticulum and Golgi apparatus must be replicated and partitioned into the daughter cells. Different mechanisms have evolved in yeasts, protozoa and metazoans to solve this problem.