Reviews & Analysis

RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. Their trafficking and activity are regulated by constitutive post-translational modifications (PTMs), including farnesylation, methylation and palmitoylation, as well as conditional PTMs, such as phosphorylation, peptidyl-proly isomerization, ubiquitylation, nitrosylation, ADP ribosylation and glucosylation.

Bone homeostasis depends on the opposing activities of osteoblasts (which form bone) and osteoclasts (which destroy bone). Recent studies have revealed the transcription factors (for example, RUNX2 and osterix) and developmental signalling pathways (including WNT and Notch signalling) that regulate the differentiation and function of osteoblasts.

Satellite cells are a heterogeneous population of stem and progenitor cells with crucial roles in muscle repair and regeneration. Although paired-box 7 (PAX7) is necessary to maintain the undifferentiated stem cell state, a requirement for PAX7 in adult satellite cells was recently challenged and remains controversial.

The autophagosome, the central organelle in macroautophagy, is constructed from a membrane template called the phagophore, to which autophagy-related (ATG) proteins are hierarchically recruited. Recent findings suggest that non-canonical autophagy may also occur in the absence of these key autophagy proteins.

Cells use molecular motors to position and segregate organelles. Recent studies show that class V myosins function as actin-based cargo transporters in yeast, moving the vacuole, peroxisomes and secretory vesicles. There is also increasing evidence in vertebrate cells that class V myosins can serve as short-range, point-to-point organelle transporters rather than just tethering organelles to actin.

X-chromosome inactivation (XCI) celebrated its golden anniversary this year. This Review looks back on key discoveries for how XCI is achieved and highlights how the cell biological mechanisms underlying XCI provide an exemplary model for the control of gene expression.

Trithorax group (TrxG) proteins, which activate transcription, have lived in the shadow of their repressive counterparts, the Polycomb group (PcG) proteins. Recent advances have revealed roles for TrxG proteins in the epigenetic regulation of the cell cycle, senescence, DNA damage and stem cell biology.

To maintain chromosome superstructure and integrity, topoisomerases resolve specific DNA superstructures or intermediates that arise from processes such as DNA repair, transcription and replication, and chromosome compaction. Despite decades of study, new insights into the cellular function and regulation of topoisomerases, as well as their use as therapeutic targets, continue to emerge.

Although the multivesicular body (MVB) is classically defined as an intermediate that delivers material for lysosomal degradation, its role in the sequestration of glycogen synthase kinase 3 during WNT signalling has revealed a positive influence of this organelle in signalling control. This Opinion article proposes that this function of MVBs as a signalling organelle is physiologically relevant during development and may be common to diverse signalling pathways.

Cells generate distinct microtubule subtypes by expressing different tubulin isotypes and through tubulin post-translational modifications, such as detyrosination, acetylation, polyglutamylation and polyglycylation. The recent discovery of enzymes responsible for many of these modifications has shown how they may regulate microtubule functions.

The characterization of the Get pathway, which directs the post-translational insertion of tail-anchored proteins into the membrane of the endoplasmic reticulum (ER), has been driven forward by structural studies and has revealed important parallels and distinctions with the classic co-translational pathway for ER membrane protein insertion.

Advances in biosensor technology have made it possible to simultaneously study the activation of multiple signalling network components in the same cell. This approach has been enhanced by novel computational approaches (referred to as computational multiplexing) that can reveal relationships between network nodes imaged in separate cells.

Caspase 8 initiates apoptosis but also has non-apoptotic roles during embryonic development and for immune cell proliferation. Recent findings indicate that the non-apoptotic functions of caspase 8 are defined by the suppression of receptor-interacting protein kinase 3 (RIPK3), a kinase that triggers programmed necrosis.

The N-end rule defines the protein-destabilizing activity of a given amino-terminal residue following its post-translational modification. The N-end rule pathway is emerging as a major cellular proteolytic system, and recent studies provide insights into its components, substrates and functions, as well as the structural basis of substrate recognition.

Microtubule nucleation is regulated by the γ-tubulin small complex (γTuSC) and the γ-tubulin ring complex (γTuRC). Recent structural work, including the crystallographic analysis of γ-tubulin complex protein 4 (GCP4), provides new insights into the mechanism of γTuRC-based microtubule nucleation, confirming the hypothesis that the γTuRC functions as a microtubule template.

The diverse components of the nucleoskeleton provide physical links, and allow communication, between the cytoskeleton and the nucleus. Together, they form dynamic networks that regulate the shape and mechanical properties of the nucleus and control nuclear function, including gene expression.

The differentiation of adipocytes from mesenchymal stem cells, known as adipogenesis, occurs in two stages, commitment and terminal differentiation, both of which are tightly regulated by mechanical and molecular cues. A better understanding of the underlying mechanisms may identify therapeutic targets for metabolic diseases.

Researchers from across the field consider the new concepts that have emerged during the past decade of molecular cell biology research, and the key challenges still to be met.

In the past 10 years, great progress has been made in the development of fluorescent proteins, including green fluorescent protein (GFP) and GFP-like proteins. Using these proteins together with a range of techniques has furthered our understanding of protein movement and protein–protein interactions.

This year marks the thirtieth anniversary since embryonic stem (ES) cells were first isolated from mouse blastocysts. In this Timeline, one of the scientists to isolate mouse ES cells in 1981 gives a personal account of the ideas that led to, and followed, this milestone.