Reviews & Analysis

Alan Turing showed that spatial patterns can be generated when two morphogens diffuse and react. Although he realized the importance of mechanics, it has only recently become clear that mechanical processes (forces and flows generated by motors) can also contribute to patterning when coupled to chemical reactions.

Muscle differentiation during development is regulated by transcription factor networks and microRNAs, and postnatal changes in muscle phenotype and mass are controlled by anabolic and catabolic signalling. Recent studies have elucidated the hierarchies of these signalling networks and have identified proteins that act both during development and in postnatal adaptation.

The ADP-ribosylation factor (ARF) and ARF-like (ARL) family of G proteins, which are known to regulate membrane traffic and organelle structure, are emerging as regulators of diverse processes, including lipid and cytoskeletal transport. Although traditionally viewed as part of a linear signalling pathway, ARFs and their regulators must now be considered to exist within functional networks, in which both the 'inactive' ARF and the regulators themselves can mediate distinct effects.

The improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have developed strategies for eliminating mitosis-incompetent cells, one of which is mitotic catastrophe. From a functional perspective, mitotic catastrophe can be defined as an oncosuppressive mechanism that precedes (and is distinct from) apoptosis, necrosis or senescence.

Cells exist within a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. Disrupting these cues compromises tensional homeostasis, which suggests that there is complex interplay between the extracellular microenvironment and cellular function. As alterations in the extracellular matrix can sustain perturbed tensional homeostasis, it serves as a mechanically based memory-storage device.

Centromeric chromatin differs from bulk chromatin in many aspects, including a distinct organization and the presence of different histone variants. Studies have focused on elucidating the molecular and physical architecture of centromeric chromatin, as well as the properties that make it invaluable during chromosome segregation in mitosis.

Transcription termination is one of the least-understood processes in gene expression. However, recent studies have revealed common themes and principles between models of RNA polymerase II (Pol II) termination, including the poly(A)-dependent and Sen1-dependent pathways, and provided insight into the role of Pol II carboxy-terminal domain phosphorylation in this process.

In 1971, Günter Blobel and David Sabatini formulated the signal hypothesis, which proposed that proteins contain signal sequences that target them for secretion. Over the past 40 years this concept has expanded, and topogenic signals are now known to target proteins to many parts of the cell.

In the ubiquitin network, a multitude of ubiquitin species is constantly decoded by ubiquitin-binding domains. To properly coordinate biological events, ubiquitylation depends on strict spatiotemporal regulation, which is achieved by compartmentalization, sequential series of ubiquitylation events and crosstalk with other post-translational modifications.

The initiation of translation in eukaryotes can be impeded by secondary structures in the mRNA upstream of the initiation codon. There is increasing evidence that several helicases act in concert to overcome such structures and to promote processive movement of the 40S ribosome subunit.

Cilium assembly requires the coordination of motor-driven intraflagellar transport, membrane trafficking and import of cilium-specific proteins through a barrier at the ciliary transition zone. Recent findings provide insights into how cilia might assemble and disassemble in synchrony with the cell cycle and achieve a steady-state length.

The genome encodes thousands of small RNAs that interact with PIWI proteins; these PIWI-interacting RNAs (piRNAs) mediate silencing of transposable elements and thereby protect the genome. New insights are being gained into the formation and functions of piRNAs, and where they exert their action in the cell.

The p53 family of transcription factors have diverse roles during development and in cancer. However, there is increasing evidence that their ancestral function may have been to regulate unique aspects of maternal fertility.

Shoot branching is regulated by three classes of plant hormones, auxins, strigolactones (or derivatives) and cytokinins. In the past decade, two models — the auxin transport canalization-based model and the second messenger model — have been formulated to explain the mechanisms of bud activation and shoot branching control.

Computational morphodynamics has provided great insights into the highly dynamic process of plant development. This is because it combines live imaging to observe development as it happens, image processing to extract data, and computational modelling to test hypotheses against quantitative information.

Asymmetric cell division is essential in many organisms, as it generates different cell types and maintains stem cell pools. The identification of key molecular players, and a comparison with the pathways in animals, allows a better mechanistic understanding of asymmetric cell division in plants and algae.

The signalling activity of cell adhesion molecules (CAMs) such as cadherins, immunoglobulin-like CAMs or integrins has been considered a direct consequence of their adhesive properties. However, in some cases CAMs can activate signalling in the absence of cell adhesion, which significantly extends their range of biological activities.

The cyclic AMP-responsive element-binding protein (CREB) is phosphorylated in response to a wide variety of signals, and it functions in concert with cAMP-regulated transcriptional co-activators (CRTCs). CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues.

Single-molecule techniques, such as atomic force microscopy, single-molecule fluorescence microscopy and optical tweezers, have helped resolve the mechanisms behind the power strokes, processive steps and forces of cytoskeletal motors. Such techniques might also reveal how motors are integrated into composite mechanical machines to generate complex functions in cells.

HTRA proteases perform a variety of protein quality control functions that are of key importance to cell fate. This Review discusses the emerging physiological implications and unique architectural and mechanistic features of bacterial, plant and mammalian HTRAs.