Reviews & Analysis

Chromosome segregation during cell division is facilitated by the kinetochore, which attaches chromosomes to spindle microtubules and relays the microtubule-binding status to the spindle assembly checkpoint (SAC). How kinetochore-dependent processes ensure faithful chromosome segregation is coming to light, as are the essential roles of the KMN network and kinase–phosphatase signalling.

The heart undergoes physiological hypertrophy in response to developmental signals and increased workload. The structural and molecular characteristics of physiological cardiac hypertrophy are now being elucidated, as are the endocrine effectors and associated signalling pathways that regulate it.

The nuclear A-type and B-type lamins, key components of the lamina underlying the nuclear envelope, have been linked to the regulation of several nuclear processes. However, studies in mice have questioned the essentiality of these lamins and have provided new understanding of how lamins function in different cells and tissues.

Sumoylation is a highly regulated process that is counteracted by specialized enzymes known as small ubiquitin-related modifier (SUMO) proteases. The recent discovery of novel SUMO proteases, together with new findings for established SUMO proteases, has led to augmented appreciation of this enzyme family.

In addition to regulating the cascades leading to cell death, mitochondria detect cell stress signals (for example, viral infection) and themselves emit danger signals in response to perturbations of homeostasis to trigger cell-intrinsic or systemic responses. They can therefore be considered as master regulators of danger signalling.

The chromosomal passenger complex (CPC), which is formed by inner centromere protein (INCENP), borealin, survivin and Aurora B kinase, targets to different locations at different times during mitosis. As it regulates key events at each of these locations, the CPC can be considered as a master regulator of mitosis.

Since the discovery of WNTs 30 years ago, it has become clear that this signalling pathway is incredibly complex, using more than 15 receptors and co-receptors. What has emerged is that these proteins form higher-order ligand–receptor complexes that transduce downstream signalling and influence numerous cellular processes.

The multiprotein nuclear pore complexes (NPCs) that mediate nucleocytoplasmic transport are universal and essential for cell viability. However, cell type-specific expression of particular NPC components and specialized NPC functions now point towards a previously unrecognized heterogeneity in these ancient pores.

Nonsense-mediated decay (NMD) is one of the surveillance pathways that ensure fidelity in gene expression by recognizing and degrading aberrant mRNAs. How the factors involved in NMD discriminate between normal and prematurely terminated mRNAs, and how they carry out their functions downstream of recognition, has been the subject of intense investigation.

Worldwide increases in life expectancy have been paralleled by a greater prevalence of chronic and age-associated disorders, particularly of the cardiovascular, neural and metabolic systems. Patient-specific induced pluripotent stem (iPS) cells are finding applications in disease modelling, drug testing and drug discovery, thus enabling researchers to undertake studies for treating diseases 'in a dish'.

The collective migration of border cells in the Drosophila melanogaster ovary has become a key model for dissecting the mechanisms that govern the coordinated movement of groups of cells. This has implications for our understanding of migration in diverse contexts, including during wound healing and tumour metastasis.

Like nuclear DNA, mitochondrial DNA possesses multiple pathways that function to preserve its integrity following exogenous insults or errors during replication. Because the candidate proteins involved are similar to those carrying out nuclear DNA repair, elucidating the contribution of each repair protein has been challenging.

The activity of protein kinases is regulated by domains that are associated with the kinase core, by interacting proteins and by their incorporation into large macromolecular complexes. Thus, understanding kinase signalling requires the structural characterization of entire complexes, as exemplified by studies of cyclic AMP-dependent protein kinase (PKA).

The basic elements of the transforming growth factor-β (TGFβ) pathway came to light more than a decade ago. Since then, the multifunctional nature and medical relevance of this pathway have relentlessly been elucidated. The old mystery of how the context determines the cellular response to TGFβ and its many malfunctions is only starting to be unravelled.

The characterization of dynamic contacts that form between the endoplasmic reticulum and mitochondria have highlighted the different ways in which the functions of these organelles can be coordinated. These structures may also allow co-regulation of distinct processes.

STIM proteins sense subtle changes in the levels of endoplasmice reticulum (ER)-stored Ca²⁺ and respond by regulating extracellular Ca²⁺entry and cell signalling. New structural and functional data have shed light on the role of STIM proteins as stress sensors.

Like all cell types, stem cells are subject to DNA damage, which results in the activation of checkpoint proteins, for example p53. These checkpoint responses lead to the clearance of damaged cells by cell-intrinsic and cell-extrinsic mechanisms, preventing carcinogenesis, but may also impair stem cell and tissue maintenance, thereby promoting ageing.

Ca²⁺ uptake through specialized transporters allows mitochondria to act as buffers of intracellular Ca²⁺ levels. Moreover, mitochondrial Ca²⁺ signalling regulates vital processes, including metabolism and cell death. Therefore, mitochondrial Ca²⁺signalling remains at the epicentre of cell biological research.

Ubiquitin can form eight structurally distinct chain types. Recent advances have elucidated the mechanisms of linkage-specific chain assembly, recognition and hydrolysis. The cellular roles of the six 'atypical' ubiquitin chains (linked via Lys6, Lys11, Lys27, Lys29, Lys33 or Met1 of ubiquitin) are beginning to emerge, highlighting how they can each act as independent post-translational modifications.

Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells use a complex network of genetic and epigenetic pathways to maintain a delicate balance between self-renewal and multilineage differentiation. Studies using high-throughput genomic tools suggest that there is extensive crosstalk among epigenetic pathways that function at the level of DNA, histone and nucleosome. Mapping of higher-order chromatin structures and chromatin–nuclear matrix interactions provides insights into the three-dimensional organization of the genome and can reveal new rules of gene regulation.