Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
The kinesin-4 motor protein Kif7 regulates Hedgehog signalling at cilia in mammals by controlling the activity of Gli transcription factors. Kif7 is now found to inhibit microtubule growth to restrict and coordinate the length of axonemal microtubules at the ciliary tip. Such Kif7-mediated organization of the ciliary tip compartment regulates Gli activity and is proposed to be required for correct Hedgehog signalling.
Clathrin-independent endocytosis removes membrane receptors and other proteins from the cell surface, yet the mechanisms controlling this process remain unclear. Galectin-3 is now shown to regulate the biogenesis of a subpopulation of clathrin-independent carriers (CLICs). Galectin-3 binds to glycosylated cargo proteins and interacts with membrane glycosphingolipids to induce membrane deformation and CLIC formation.
Cadherin-containing cell–cell junctions respond to intercellular tension by increasing their size, strength and complexity. The mechanical regulation of cadherin adhesions is now shown to involve myosin-dependent tension in the cortical actomyosin cytoskeleton. This reduces actin turnover to decrease the mobility of cadherin molecules and increase their concentration at junctions.
Despite the widespread occurrence of aneuploidy in cancer cells, the molecular causes for chromosomal instability are not well established. Cyclin B2 is now shown to control a pathway — involving the centrosomal kinases aurora A and Plk1 and the tumour suppressor p53 — the alteration of which causes defective centrosome separation, aneuploidy and tumour development.
Pluripotent embryonic stem cells (ESCs) can be derived from blastocyst-stage mouse embryos. However, the exact in vivo counterpart of ESCs has remained elusive. A combination of expression profiling and stem cell derivation identifies epiblast cells from late-stage blastocysts as the source, and functional equivalent, of ESCs.
The degradation of dysfunctional proteins and organelles by autophagy is important for cell viability. Dikic and co-authors discuss how cargo selection is achieved during selective autophagy and how the processes involved in cargo delivery are related to membrane trafficking pathways.
Puisieux et al. discuss endothelial to mesenchymal transition (EMT)-inducing transcription factors in tumorigenesis. They explore how EMT contributes not only to tumour progression through its roles in invasion and metastasis, but also to malignant transformation and early tumour development by impinging on tumour suppressive pathways and cell differentiation states.
Using in vitro reconstitution systems, three studies shed light on the interactions of Atg8 family proteins with cargo receptors and components of the basal autophagy machinery. The results have important mechanistic implications for selective macroautophagy, scaffold formation and spatio-temporal organization of the lipidation process during autophagosome formation.
Heterogeneity in tumour cell properties underlies many treatment failures. Understanding the sources of such heterogeneity has proved to be challenging, but remains critical to improving patient outcomes. Integrin αvβ3 expression in multiple types of solid tumour stem cells is now shown to control a pro-survival pathway that contributes to therapy resistance.
Multipolar spindles are a feature of cancer cells often associated with chromosomal aberrations. In the final Review in our Series on Genomic Instability, Logarinho and Maiato discuss how multipolar spindles form, with an emphasis on the role of the loss of spindle pole integrity in this process.
Genetically encoded and post-translationally generated variations of tubulin C-terminal tails give rise to extensive heterogeneity of the microtubule cytoskeleton. The generation of different tubulin variants in yeast now demonstrates how single amino-acid differences or post-translational modifications can modulate the behaviour of selected molecular motors.
Although human cancers exhibit intratumour heterogeneity, the influence of the tumour environment on this property is unclear. Single basal-like mammary epithelial cells are now shown to engage a dynamic TGFBR3–JUND signalling circuit in an extracellular-matrix-dependent manner. Cell transition between the distinct gene expression states underlying this circuit alters their properties and may modulate their propensity to malignancy.
New blood vessels sprout from existing vasculature to ensure vascularization of developing organs and tissues. A combination of computational modelling and experimental analysis shows that sprout elongation is mediated by differential adhesion dynamics among endothelial cells. The adhesiveness of an individual endothelial cell is governed by VEGF and Notch signalling.
Repair of a chromosome break can result in part of a chromosome attaching to a different chromosome, causing gene deregulation and disease. Roukos and Misteli discuss the spatial aspect of chromosome translocation and the role of DNA repair pathways in this process.
Defective asymmetric cell divisions of stem and progenitor cells are associated with tumorigenesis by a largely unknown mechanism. A signalling axis involving Snail, microRNA-146a and Numb is now shown to regulate the switch between symmetric and asymmetric cell division in colorectal cancer stem cells.
Collective cell migration depends on multicellular mechanocoupling between leader and follower cells to coordinate traction force and position change. Co-registration of Rho GTPase activity and forces in migrating epithelial cell sheets now shows how RhoA controls leader–follower cell hierarchy, multicellular cytoskeletal contractility and mechanocoupling, to prevent ectopic leading edges and to move the cell sheet forward.
Correct regulation of insulin secretion by the pancreas is crucial for organismal function and survival. The AMPK-related kinase SIK2 (salt-inducible kinase 2) is now shown to be stabilized in pancreatic β-cells following glucose stimulation, leading to improved systemic glucose homeostasis by regulating cellular calcium flux and insulin secretion.
In the second Review in our Genomic Instability series, Rudolph and colleagues discuss how the genomic damage that accumulates during ageing affects stem cell function through both cell-intrinsic and cell-extrinsic mechanisms.
Emerging data support that RNA methylation plays important roles in RNA processing and metabolism. The methyltransferases Mettl3 and Mettl14 are shown to catalyse N6-methyladenosine (m6A) RNA modification in embryonic stem cells (ESCs). This m6A modification controls RNA metabolism and functions to destabilize mRNAs encoding developmental regulators to help sustain ESC self-renewal.
Epithelial cell layers need to be tightly regulated to maintain their integrity and correct function. Cell integration into epithelial sheets is now shown to depend on the N-WASP-regulated stabilization of cortical F-actin, which generates distinct patterns of apical–lateral contractility at E-cadherin-based cell–cell junctions.
