Review Articles in 2011

RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. Their trafficking and activity are regulated by constitutive post-translational modifications (PTMs), including farnesylation, methylation and palmitoylation, as well as conditional PTMs, such as phosphorylation, peptidyl-proly isomerization, ubiquitylation, nitrosylation, ADP ribosylation and glucosylation.

Bone homeostasis depends on the opposing activities of osteoblasts (which form bone) and osteoclasts (which destroy bone). Recent studies have revealed the transcription factors (for example, RUNX2 and osterix) and developmental signalling pathways (including WNT and Notch signalling) that regulate the differentiation and function of osteoblasts.

Cells use molecular motors to position and segregate organelles. Recent studies show that class V myosins function as actin-based cargo transporters in yeast, moving the vacuole, peroxisomes and secretory vesicles. There is also increasing evidence in vertebrate cells that class V myosins can serve as short-range, point-to-point organelle transporters rather than just tethering organelles to actin.

X-chromosome inactivation (XCI) celebrated its golden anniversary this year. This Review looks back on key discoveries for how XCI is achieved and highlights how the cell biological mechanisms underlying XCI provide an exemplary model for the control of gene expression.

Trithorax group (TrxG) proteins, which activate transcription, have lived in the shadow of their repressive counterparts, the Polycomb group (PcG) proteins. Recent advances have revealed roles for TrxG proteins in the epigenetic regulation of the cell cycle, senescence, DNA damage and stem cell biology.

To maintain chromosome superstructure and integrity, topoisomerases resolve specific DNA superstructures or intermediates that arise from processes such as DNA repair, transcription and replication, and chromosome compaction. Despite decades of study, new insights into the cellular function and regulation of topoisomerases, as well as their use as therapeutic targets, continue to emerge.

Cells generate distinct microtubule subtypes by expressing different tubulin isotypes and through tubulin post-translational modifications, such as detyrosination, acetylation, polyglutamylation and polyglycylation. The recent discovery of enzymes responsible for many of these modifications has shown how they may regulate microtubule functions.

The characterization of the Get pathway, which directs the post-translational insertion of tail-anchored proteins into the membrane of the endoplasmic reticulum (ER), has been driven forward by structural studies and has revealed important parallels and distinctions with the classic co-translational pathway for ER membrane protein insertion.

The N-end rule defines the protein-destabilizing activity of a given amino-terminal residue following its post-translational modification. The N-end rule pathway is emerging as a major cellular proteolytic system, and recent studies provide insights into its components, substrates and functions, as well as the structural basis of substrate recognition.

Microtubule nucleation is regulated by the γ-tubulin small complex (γTuSC) and the γ-tubulin ring complex (γTuRC). Recent structural work, including the crystallographic analysis of γ-tubulin complex protein 4 (GCP4), provides new insights into the mechanism of γTuRC-based microtubule nucleation, confirming the hypothesis that the γTuRC functions as a microtubule template.

The diverse components of the nucleoskeleton provide physical links, and allow communication, between the cytoskeleton and the nucleus. Together, they form dynamic networks that regulate the shape and mechanical properties of the nucleus and control nuclear function, including gene expression.

The differentiation of adipocytes from mesenchymal stem cells, known as adipogenesis, occurs in two stages, commitment and terminal differentiation, both of which are tightly regulated by mechanical and molecular cues. A better understanding of the underlying mechanisms may identify therapeutic targets for metabolic diseases.

In the past 10 years, great progress has been made in the development of fluorescent proteins, including green fluorescent protein (GFP) and GFP-like proteins. Using these proteins together with a range of techniques has furthered our understanding of protein movement and protein–protein interactions.

The ability of methylarginine sites to serve as binding motifs for Tudor proteins, and the functional significance of this, is now becoming clear. Tudor proteins are thought to interact with methylated PIWI proteins and regulate the PIWI-interacting RNA pathway in the germ line.

Haematopoietic stem cell function is tightly controlled to maintain haematopoietic homeostasis, in part by specialized cells and factors that constitute the haematopoietic 'niche'. Recent discoveries have engendered a new appreciation for the dynamic nature of the niche, identifying novel cellular and acellular niche components and uncovering fluctuations in their importance over time.

The coordinated control of endothelial cell behaviour is critical for blood vessel morphogenesis. Recent data reveal elaborate mechanisms that fine-tune key signalling pathways (such as the vascular endothelial growth factor and Notch pathways) to control endothelial cell behaviour during blood vessel sprouting (angiogenesis).

Ubiquitylation regulates essentially all of the intracellular processes in eukaryotes by modifying numerous cellular proteins in a spatially and temporally controlled manner. Many components of the ubiquitin–proteasome system are themselves modified by ubiquitylation; this regulates their activity or targets them for degradation.

Keratinocytes of the epidermis undergo several transformations as they differentiate and migrate outwards in the tissue to maintain epidermal homeostasis. Dynamic changes in adhesive junctions and the cytoskeleton of keratinocytes are a driving force in this morphogenesis.

Four models have been proposed to explain growth control mediated by the morphogen Decapentaplegic in the fly imaginal disc. Recent findings have allowed a more careful evaluation of these models and may offer insights into morphogenetic growth control in other systems.

During mammary gland development, signalling networks between epithelial cells and several cell types in the stroma are orchestrated together with mechanical cues and collective cell migration events to drive morphogenesis.