Reviews & Analysis

Polycomb group (PcG) proteins constitute a conserved gene silencing system with widespread roles in multicellular development, stem cell biology and cancer. Recent studies suggest that PcG-mediated gene silencing may involve histone modifications and a possible block in transcriptional elongation.

It is now recognized that cell signalling and endocytic membrane trafficking are intimately and bidirectionally linked in animal cells. The mechanistic and functional principles that underlie the relationship between these cellular processes are becoming increasingly evident across many systems.

Clathrin-mediated endocytosis dynamically regulates the composition of the plasma membrane in eukaryotic cells by internalizing transmembrane proteins, bound ligands and lipids. To regulate the uptake of a vast array of cargo molecules, specific sorting signals in cargoes are decoded by different cytosolic adaptor proteins.

Studies of cargo proteins that are internalized independently of clathrin have revealed new pathways and mechanisms of endocytic recycling. Precise temporal and spatial regulation of recycling pathways is crucial for various cellular processes, including cytokinesis, cell adhesion, morphogenesis, cell fusion, learning and memory.

The reconstitution of biological processes from purified components is a powerful approach to understanding the principles that govern cellular organization. The recent development of new experimental techniques is enabling the reconstitution of increasingly complex cellular systems.

Lysosomes are the primary catabolic compartments of eukaryotic cells. They degrade extracellular material that has been internalized by endocytosis and intracellular components that have been sequestered by autophagy. Emerging evidence suggests that there are multiple lysosomal delivery pathways that together allow the regulated and sequential deposition of lysosomal components.

The Bicoid (BCD) morphogen gradient was thought to be formed by diffusion of the protein away from the anterior pole of theDrosophila melanogasterembryo. A new study shows that a bcd mRNA gradient prefigures the protein gradient and proposes a model that combines active mRNA transport with local BCD translation.

A large superfamily of deubiquitinases (DUBs) has a key role in both determining protein stability and terminating ubiquitin-dependent signal transduction. Structural and biochemical studies have started to reveal the underlying principles by which DUB substrate specificity is achieved.

Natural antisense transcripts are frequently functional and are involved in regulating gene expression. The authors summarize the proposed actions of antisense transcript into four models, each corresponding to a putative regulatory mechanism for a subset of antisense transcripts.

The life cycle of an organism is characterized by phases of reprogramming and differentiation during development from the zygote to the adult organism. Lineage-determining transcription factors and epigenetic mechanisms form inseparable strands that regulate pluripotency and early cell lineage decisions.

Directional cell migration is achieved by forming and stabilizing protrusions or lamellipodia at the leading edge of the cell. Many factors and processes can affect leading edge formation, and they often depend on local regulation of the Rho family of GTPases.

Rab GTPases control intracellular vesicle traffic by acting as regulatable switches that recruit effector molecules when in their GTP-bound form. The functional coupling between multiple Rab GTPases ensures the spatiotemporally coordinated regulation of vesicle traffic.

The collective migration of cells as cohesive groups is prevalent during embryogenesis, organ development, wound repair and tumour invasion. The mechanisms that underlie different forms of collective cell migration are not well understood, but some general principles are emerging.

The mitotic checkpoint is a cell cycle control mechanism that guards against chromosome missegregation and the subsequent production of aneuploid daughter cells. Although aneuploidy is a common characteristic of tumours, it can suppress tumorigenesis in certain genetic contexts and cell types.

The cytoplasmic and nuclear steps of the Wnt signalling pathway are fairly well understood. New insights into how secreted Wnt ligands stimulate receptor-mediated signalling have shown an unexpected diversity of Wnt receptors and further complexity in cellular responses.

The growth of microtubules is accompanied by large fluctuations in rates and abrupt transitions between phases of growth and shrinkage. The authors propose that fluctuations in the length of the GTP–tubulin cap at the microtubule end could be the main source of variation.

Studies of autophagy in yeast have identified a family of autophagy-related (Atg) proteins, which are required for membrane formation in autophagy. The dynamic assembly of Atg proteins into the pre-autophagosomal structure dictates the localization and activity of the autophagic machinery.

In interphase, chromosomes are associated with proteins and RNAs that participate in many metabolic processes. During mitosis, these components might inhibit chromosome segregation or reduce its fidelity. The author proposes the existence of a molecular mechanism that eliminates unwanted components from mitotic chromosomes.

Compositionally and functionally distinct RNA granules are found in the cytoplasm of somatic and germ cells. The components of most RNA granules are in a dynamic equilibrium, thereby allowing rapid shifts between the translation, storage and decay of RNAs.

Synthetic biology combines the investigative nature of biology with the constructive nature of engineering. A 'first wave' in the field has led to the creation of genetic devices and small modules that are constructed from these devices. Now, a 'second wave' is required to develop effective strategies for assembling devices and modules into intricate customizable larger scale systems.