Reviews & Analysis

The phosphodiesterase autotaxin (ATX) produces the lipid mediator lysophosphatidic acid (LPA) to regulate diverse processes, including cell migration and proliferation. Studies of the structure of ATX may shed new light on how ATX recognizes its substrates and associates with the cell surface to promote specificity in LPA signalling.

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.

RNA helicases of the DEAD box family are highly conserved enzymes with many roles in gene expression. Structural and mechanistic studies are uncovering the basis of their actions and have revealed roles not only in RNA unwinding but also in the remodelling of RNA–protein complexes and in the clamping of RNA to allow nucleation of larger complexes.

Clathrin-mediated endocytosis is a modular process that involves core and accessory adaptor proteins that package cargoes into vesicles, ultimately leading to their uptake. It is essential for many physiological processes in higher eukaryotes, including signal termination and exocytosis, so its components are rarely associated with disease.

RHO-specific guanine nucleotide dissociation inhibitors (RHOGDIs) had long been considered to be passive inhibitors of RHO GTPases, 'locking' them in an inactive state. However, recent findings suggest that they have integral roles in regulating RHO GTPases, controlling aspects such as stability, expression, activity and membrane localization.

In eukaryotes, RNA polymerases I, II and III synthesize RNAs, which are essential for life. Remarkably, plants have evolved two additional multisubunit RNA polymerases, RNA polymerases IV and V, to orchestrate non-coding RNA-mediated gene silencing processes. Their subunit compositions reveal that they evolved as specialized forms of RNA polymerase II.

The regulation of mitotic exit requires the rapid reversal of mitotic phosphorylation on a broad range of substrates. This requires not only inactivation of mitotic kinases but also activation of protein phosphatases, which work in regulatory networks to ensure that an interphase cell is correctly established.

This timeline article pays tribute to the late James Fred 'Paulo' Dice, whose vision of selective protein degradation in lysosomes led to the discovery of chaperone-mediated autophagy.

Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to — and degradation of — the extracellular matrix. Progress has been made in our understanding of the regulation and function of these structures, and their role in human disease.

The regulation of apoptosis is essential for cell homeostasis and the survival of multicellular organisms, and excessive or diminished apopotosis can contribute to various diseases. The post-translational modification of apoptotic proteins by ubiquitylation is a key regulatory mechanism of cell death signalling cascades. Targeting apoptotic regulatory proteins in the ubiquitin proteasome system might afford clinical benefits.

Differentiated cells can become pluripotent through reprogramming by nuclear transfer, cell fusion and induced pluripotent stem cell technology. The characteristics of reprogramming by nuclear transfer and cell fusion suggest that they occur in a deterministic, rather than a stochastic, manner.

The kinetochore is a large complex of proteins that physically links centromeric DNA to microtubules. Recent research has identified the individual kinetochore building blocks and studied how they interact, allowing the development of a model of the overall architecture of the kinetochore.

The APC/C (anaphase-promoting complex, also known as the cyclosome) is an E3 ubiquitin ligase that ensures temporal order of the cell cycle by degrading different cell cycle regulators at specific time points. Recent studies have provided insights into how the APC/C recognizes its substrates and how it is itself regulated.

The production of mature and export-competent messenger ribonucleoproteins (mRNPs) is a multistep process that is regulated in a spatial and temporal manner. Recent studies suggest that post-translational modifications play a part in coordinating the co-transcriptional assembly, remodelling and export of mRNP complexes through nuclear pores.