Review Articles in 2010

ATPases transport ions into and out of cells to maintain ion concentration gradients and control aspects of the cellular environment, such as pH. Structural studies of the Na⁺,K⁺-ATPase, which transports Na⁺ and K⁺, and the H⁺-ATPase, which transports H⁺, have provided insights into their functions in eukaryotic cells.

There is increasing evidence that an 'open' chromatin state contributes to maintenance of pluripotency in stem cells, and that this requires regulation of both the global chromatin state and local repression of transcription. This regulation may also be relevant for chromatin control during reprogramming or during tumorigenesis.

In eukaryotes, the target of rapamycin (TOR) protein kinase simultaneously senses energy, nutrients and stress (and growth factors in metazoans) to regulate cell growth and division. Advances in our understanding of the regulation and functions of mammalian TOR (mTOR) are revealing its involvement in diabetes, cancer and ageing.

Mitochondria and chloroplasts import the vast majority of their proteins across two membranes. Although the import and initial sorting of precursor proteins is mediated by translocases that are functionally similiar in the outer membrane of both organelles, they each have a unique mode of translocation.

Conjugation of the ubiquitin-like protein SUMO to proteins regulates many biological processes. Insights are emerging into mechanisms that regulate the SUMO modification pathway, including other post-translational modifications. Many substrates also harbour additional characteristics that facilitate their modification.

The continuous fusion and fission of mitochondria is important for their inheritance and function. The core components of the fusion and fission machineries, and the mechanisms that regulate these processes, have recently been elucidated and found to be integral for the maintenance of cellular quality control.

Cells divide asymmetrically to generate diverse cell types during development. Research over the past 10 years has furthered our understanding of asymmetric cell division in invertebrates. Furthermore, this work has uncovered connections between asymmetric cell division and tumorigenesis and a role for this process in stem cell biology.

The MET receptor promotes tissue remodelling by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation, which can be exploited in regenerative medicine and cancer therapy.

Mammalian prions are typically associated with the development of neurodegenerative diseases. However, prions in fungi act as epigenetic determinants. The similarities between mammalian and fungal prions suggest that, rather than being a biological anomaly, prions might instead function as regulators of cell phenotype.

Organisms can anticipate environmental changes owing to an intrinsic molecular clock. Our molecular understanding of circadian oscillators has advanced over the past decade with the deployment of systems biology approaches, enabling a multiscale view of circadian systems from the molecular level to the intact organism.

Focal adhesion kinase (FAK) is a scaffold and tyrosine kinase protein that binds to itself and cellular partners through its four-point-one, ezrin, radixin, moesin (FERM) domain. Recent structural work reveals how regulatory proteins activate FAK by binding to its FERM domain, enabling it to coordinate diverse cellular responses.

Proteomes are typically analyzed by mass spectrometry, and recent advances have greatly increased the fraction of the proteome that can be identified and quantified in a single study. Mapping complete proteomes and using such maps for targeted quantitative proteomics will increase the impact of proteomics on biological and clinical research.

The aggregation of misfolded proteins is associated with the perturbation of cellular function and ageing. However, protein aggregation can also be a regulated process that deposits aggregates at specific cellular sites. This is protective as it facilitates aggregate solubilization, refolding and degradation by the protein quality-control network.

Metabolic pathways such as glycolysis and the pentose phosphate pathway communicate to cell cycle and apoptotic effectors, including D-type cyclins, CDKs, APC, p53, caspase 2 and BCL-2 proteins. The importance of this crosstalk is emphasized by the role of metabolic aberrations in the aetiology of disease.

In multicellular organisms, DNA replication adapts to variations in growth conditions, DNA damage and chromatin organization changes associated with cell differentiation. Therefore, only a subset of replication origins is used at each cell cycle, the choice of which is controlled by various factors including epigenetic mechanisms and gene expression.

Ten years ago, the cell biological role of lipid rafts was controversial owing to limited methodology and confusing nomenclature. Through technical advances, our concept of lipid rafts has evolved into that of dynamic nanoscale assemblies that can be stabilized to control signalling and membrane trafficking.

Although necrosis was regarded as an uncontrolled mode of cell death, evidence now shows that it can be highly regulated. The initiation of programmed necrosis (necroptosis) by death receptors requires receptor-interacting protein 1 (RIP1) and RIP3, and its execution involves the active disintegration of mitochondrial, lysosomal and plasma membranes.

Non-vesicular lipid transport between intracellular membranes can be mediated by spontaneous lipid transfer or lipid-transfer proteins (LTPs) and is crucial for maintaining the identities of different cellular membranes. Current studies focus on further understanding the mechanisms of non-vesicular lipid transport and elucidating the role of LTPs in intact cells.

Cell migration affects all morphogenetic processes and contributes to numerous diseases, including cancer and cardiovascular disease. Adhesion formation and disassembly drive the migration cycle by activating Rho GTPases, which in turn regulate actin polymerization and myosin II activity, and therefore adhesion dynamics.

Proteomic studies have led to the identification of numerous new transport components and pathways for mitochondrial protein import. Furthermore, they have revealed that protein translocases are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum.