Reviews & Analysis

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.

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.

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.

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.

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.

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.

Ubiquitylation targets proteins for degradation or other cellular fates. The HECT enzymes are E3 ubiquitin ligases, which dictate the specificity of ubiquitylation. HECTs regulate trafficking of many receptors, channels, transporters and viral proteins. Their role in metazoans is becoming clearer fromin vivostudies.

ATP-dependent chromatin-remodelling complexes are well-known regulators of transcriptional processes. Interestingly, the INO80 and SWR1 complexes also participate in a range of pathways that are involved in genome maintenance, such as DNA repair, checkpoint regulation, DNA replication, chromosome segregation and telomere stabilization.

The ubiquitin–26S proteasome system is one of the most pervasive pathways of intracellular protein regulation in plants. It controls hormone signalling, chromatin structure and transcription, tailoring morphogenesis, responses to environmental challenges, self-recognition and the battle between pathogens and their plant hosts.

The journey of the growth cone is similar to a vehicle on a road. Cytoskeletal elements form the 'motor' to move forward and provide traction on the road, whereas a 'navigator' system guides the vehicle to translate environmental signals into directional movement.

The attachment of ubiquitin-like proteins (UBLs) to proteins is a central mechanism of modulation of protein function. Enzymatic, structural and genetic studies have elucidated how mechanistically and structurally related E1 enzymes activate UBLs and selectively direct them to downstream pathways.

Ions move across cell membranes through either ion channels or ion pumps. Recently, atomic-resolution structures and high-resolution functional measurements of examples from both channels and pumps have begun to suggest that these molecules need not be as different as was once thought.

Cells have evolved complex mechanisms to control overall protein synthesis and the translation of specific mRNAs. At the heart of this process is the mammalian target of rapamycin (mTOR) signalling pathway, which senses and responds to nutrient availability, energy sufficiency, stress, hormones and mitogens to modulate protein synthesis.

The canonical Wnt pathway controls metazoan development and tissue homeostasis, and its disregulation in humans results in cancer. Transcription of Wnt target genes is regulated by nuclear β-catenin. How does β-catenin interact with chromatin to regulate Wnt target gene transcription?