Review Articles in 2013

The mechanisms that drive cell intercalation and thereby cell rearrangements during morphogenesis vary in different developmental contexts and species. Comparison of the key control steps in each case has improved our understanding of the specific parts played by adhesion and cytoskeletal changes, as well as planar cell polarity signalling.

Interactions on the mitochondrial outer membrane between members of the three subgroups of the BCL-2 protein family set the apoptotic threshold. Recent structural insights into the molecular mechanisms of this commitment to apoptosis are guiding the development of new therapeutics for cancer, and potentially also autoimmune and infectious diseases.

Renewal and repair of the intestinal epithelium depend on small populations of intestinal stem cells. Specific markers for these stem cells have recently been discovered. This advance, together with the development of new technologies to track endogenous stem cell activity and to generate new epitheliaex vivo, is shedding light on the mechanisms underlying intestinal stem cell-driven homeostasis and regeneration.

The function of 53BP1 in DNA double-strand break repair is multifaceted, and includes mediator and effector roles. New appreciation of how it is recruited to damaged chromatin, and how it exerts control on pathway choice, has cemented the central role of 53BP1 in genome stability maintenance.

The control of peroxisome biogenesis by different mechanisms, includingde novogeneration or growth and fisson of existing peroxisomes, may be coordinated to control peroxisome size and number. Dissecting this process should aid our understanding of how peroxisome dynamics are regulated, with implications for peroxisome-related diseases.

Chloroplasts are the ancestral members of the plastid organelle family. Their identity, division and biogenesis require the import of nucleus-encoded proteins and tight coordination between the organellar genetic system and the nucleocytosolic system. The ubiquitin–proteasome system also links plastid homeostasis and biogenesis to organismal development.

Lipid droplets are intracellular organelles that store oil-based reserves of metabolic energy and components of membrane lipids. Basic biophysical principles of emulsions are important for lipid droplet biology, their formation, growth and shrinkage. Such mechanisms enable cells to use emulsified oil when required. The surfactant composition at the lipid droplet surface is crucial for homeostasis and protein targeting to their surfaces.

Autophagosome biogenesis starts at the isolation membrane (also called the phagophore). Our understanding of the molecular processes that initiate the isolation membrane, the membrane sources from which this membrane originates and how it is expanded to the autophagosome membrane by autophagy-related (ATG) proteins and the vesicular trafficking machinery, is increasing.

Receptor-interacting protein (RIP1) is a key upstream regulator of signalling pathways that lead to either inflammation or cell death by apoptosis or necroptosis. Recent evidence indicates that the decision between these pathways is regulated by the ubiquitylation and deubiquitylation of RIP1, which determines its interaction with various ubiquitin-binding proteins.

In addition to their roles in chromatin regulation, long non-coding RNAs (lncRNAs) are being characterized as regulators of diverse cell biological processes, including post-transcriptional control, organization of scaffolds and cell signalling. These findings add weight to the notion that lncRNAs provide a flexible resource for rapid cellular control.

Fuelled by ATP hydrolysis, dyneins generate force and movement on microtubules in a wealth of biological processes. A model for the mechanochemical cycle of dynein is emerging, in which nucleotide-driven flexing motions within the AAA+ ring of dynein alter the affinity of its microtubule-binding 'stalk' and reshape its mechanical element to generate movement.

It is becoming clear that the stem cells from the mammalian epidermis are more heterogeneous than previously anticipated, comprising populations with specific properties and lineage preferences. There is also evidence of crosstalk between epidermal stem cells and surrounding cell populations to ensure their survival and homeostasis.

Disruption of the protein quality control system can lead to protein misfolding, inactivity and aggregation. New structural and biochemical insights into how disaggregases collaborate with co-chaperones and utilize ATP to untangle these aggregates are now being gained. This is clinically relevant, as aggregation is often linked to common neurodegenerative diseases.

Chaperones are heavy-duty molecular machines that assist nascent proteins to reach their native fold but also mediate unfolding and prevent the accumulation of toxic protein aggregates. There is an increasing structural understanding of how they might perform such large-scale rearrangements.

Damage signalling in response to DNA double-strand breaks is under tight negative regulation. These control mechanisms, which include post-translational modifications and changes in chromatin structure, ensure that pathways are spatially and temporally regulated and that they become inactivated when repair is complete.

Nuclear factor-κB (NF-κB) signalling is tightly regulated through ubiquitylation and phosphorylation of its components. Integral to this post-translational regulation is the polyubiquitin-binding protein NF-κB essential modulator (NEMO), which controls the modification of numerous NF-κB signalling proteins, such as the canonical IκB kinase (IKKs) and IKK-related kinases.

The addition or removal of poly(A) tails from the 3′ ends of eukaryotic RNAs is a key regulator of RNA stability and, consequently, of gene expression. Recent work has revealed that RNA turnover is also controlled by the addition of oligo(U) tails.

Phospho-Ser/Thr-binding domains are crucial regulators of cell cycle progression and DNA damage signalling. Progress has been made in our understanding of the motif (or motifs) that these domains connect with on their target proteins and precisely how these interactions influence the cell cycle and DNA damage response.

Cell competition occurs when cells that grow at different rates confront each other. This results in the elimination of the slower growing cells by apoptosis. Although exactly how this occurs is unclear, mechanical factors might be involved, as cell crowding within an epithelium leads to delamination and extrusion.

Fertilization triggers a complex cellular programme that leads to a totipotent mitotic embryo. The molecular mechanisms underlying the meiosis to mitosis transition include changes in sister chromatid linkages, the reintroduction of a centrosome, a shift to symmetric cell division and changes in genomic imprinting and protein expression control.