Reviews & Analysis

Three recent studies reveal unexpected functions of Rap1, a member of the shelterin complex that protects chromosome ends from the activity of DNA repair pathways. Rap1 not only protects telomeres from sister chromatid exchange, but also functions in genome-wide transcriptional regulation and NF-κB-dependent signalling, revealing new perspectives for the telomere field.

The bacterial cytoplasm is rich in filament-forming proteins, from homologues of eukaryotic cytoskeletal elements to other scaffolding and segregation proteins. We now learn that even the metabolic enzyme CTP synthase forms cytoplasmic filaments that affect bacterial cell shape.

The plasma membrane is identified as a source for the formation of autophagosomes, the double membrane vesicles that deliver intracellular components to lysosomes for their degradation.

Rab GTPases regulate the dynamics of transport carriers by participating in their translocation across the cytoplasm, and in their docking and fusion with acceptor compartments. An interaction between Golgi-associated Rab6 and myosin II has now been shown to regulate the fission of Rab6-positive carriers, illuminating a previously unappreciated role for Rab6 and the actomyosin system in carrier biogenesis.

Recognition of apoptotic cells by phagocytic cells in Caenorhabditis elegans has been something of a mystery. A secreted transthyretin-like protein, TTR-52, has been identified as a bridging molecule between apoptotic cells and CED-1 on the phagocytic cells that engulf them.

Tumour suppressors of the Forkhead box O (FoxO) family are proposed to limit tumour growth through direct transcriptional regulation. Cytosolic FoxO1 can also suppress tumour growth by triggering autophagy and ultimately cell death in a transcription-independent manner.

The importin-β-like transport receptors and RanGTP govern selective transport of proteins into the nucleus. It has now been shown that importin-β2 (alternatively called transportin1) also selectively targets the motor protein Kif17 to primary cilia. In analogy to the nucleus, RanGTP in the intraciliary compartment mediates dissociation of Kif17 from its transport receptor and thereby completes import.

Adherens junctions, the sites of cadherin-dependent cell–cell adhesion, are also important for dynamic tension sensing, force transduction and signalling. Different myosin motors contribute to adherens junction assembly and versatility in distinct ways.

Innovations in live-cell microscopy and single-molecule analysis have allowed a new direct view of nuclear messenger RNA dynamics. A new study extends previous analyses of mRNA-protein intranuclear transport and links this critical step to the kinetics of moving through nuclear pore complexes. Seeing nuclear mRNA on the move will impact future work on pore translocation and nuclear organization.

The distribution of secreted morphogens in a developing organ determines its form by instructing size, shape and pattern. Pentagone has been identified as a secreted factor that controls the distribution of the morphogen Decapentaplegic (Dpp) in the Drosophila melanogaster wing.

The balance of cohesion and remodelling is essential for the integrity and morphogenesis of epithelia. This requires adhesion and transmission of actomyosin tension, both of which are mediated by E-cadherin. The finding that actomyosin tension reinforces mechanical coupling of actin to E-cadherin through α-catenin reveals similarities with integrin regulation.

CRACR2A is a newly discovered Ca²⁺-binding protein that regulates store-operated Ca²⁺ entry (SOCE). CRACR2A enhances SOCE by promoting the binding of the endoplasmic reticulum Ca²⁺ sensor STIM to Orai, a Ca²⁺ channel located in the plasma membrane. As intracellular Ca²⁺ levels rise, CRACR2A binds Ca²⁺ and triggers SOCE inactivation by dissociating from the Orai–STIM complex.

Formation of multivesicular bodies (MVBs) from endosomes or budding of enveloped virus such as HIV-I from the plasma membrane require the ESCRT (endosomal sorting complex required for transport) complexes. An in vitro reconstitution assay unambiguously identifies the function of each ESCRT complex in the sequential events of MVB morphogenesis, from cargo clustering and membrane bud formation to sequestration of cargoes in vesicles, and fission of the vesicles into the lumen of the endosome.

Instability in the structure and number of chromosomes is a trait common to cells from most epithelial cancers. A role in chromosome segregation for a pathway previously implicated in the DNA damage response reveals new connections between the tumour suppressive processes that maintain chromosome integrity.

Although all cells within a colon cancer may harbour adenomatous polyposis coli (APC) or β-catenin mutations, activation of Wnt signalling is limited to a subpopulation of cells that display cancer stem cell properties. This activation requires a co-stimulatory signal mediated by hepatocyte growth factor, which is produced by tumour-associated myofibroblasts.

Cilia drive fluid flow in development and physiology, but this requires that all cilia in a tissue orient the same way. Earlier studies indicated that both planar cell polarity (PCP) signalling and cilia-generated fluid flows could influence ciliary orientation. We now learn how asymmetric localization of PCP proteins influences the position and orientation of cilia to control the direction of flow.

The deubiquitylating enzyme Dub3 is found to have oncogenic potential by stabilizing the Cdc25A protein phosphatase, a crucial regulator of cell-cycle progression.

Cytokinesis — the final step of mitosis in which the two daughter cells separate — requires accumulation of specific proteins and lipids at the connecting bridge to ensure cleavage by abscission. Phosphatidylinositol-3-phosphate (PtdIns(3)P), an endosomal phosphoinositide, and FYVE-CENT, a PtdIns3P-binding protein, are found in the bridge, where they contribute to the mechanism of abscission.

Peroxisomes can import large multimeric protein complexes and even 9-nm gold particles decorated with peroxisome-targeting signals. They achieve these feats of protein passage using a distinctive translocon whose highly dynamic aqueous pore can expand to accommodate the increasing girths of different peroxisome receptor–cargo complexes.