News & Views

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.

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.

Signal integration is central to the regulation of patterning during plant development. During lateral root initiation, a signalling pathway controlled by the phloem-secreted TDIF peptide is found to activate the auxin signalling pathway independently of auxin, through phosphorylation of ARF transcription factors by GSK3 (Shaggy-like) kinases.

Macroautophagy is a key regulator of cellular integrity and viability, but how the process facilitates apoptosis has remained poorly defined. It has now become clear that autophagy degrades the Fap-1 protein phosphatase, a critical negative regulator of apoptotic cell death signalled by the TNF receptor family member, Fas.

Generation of differentiated kidney cell types from pluripotent stem cells would be enormously useful for research and therapeutic purposes, but progress towards this goal has so far been limited. In three recent reports, mature kidney cell types and three-dimensional nephron-like structures were generated from pluripotent cells rapidly and efficiently. A detailed understanding of the signals that drive nephrogenesis proved critical for these achievements.

Oxidation of actin methionine residues by the oxidation–reduction enzyme Mical is known to lead to actin filament depolymerization. SelR enzymes are now shown to reduce these oxidized actin methionines, revealing a regulated redox reaction mechanism through which cells control the assembly and disassembly of actin filaments.

Centrioles duplicate only once per cell cycle in proliferating cells, whereas in multiciliated cells, hundreds of centrioles form almost simultaneously. The molecular control mechanisms that govern centriole amplification in multiciliated cells are largely unknown. Two studies highlight Deup1 and CCDC78 as key players in this process.

Calcium enters mitochondria through a dedicated channel referred to as the mitochondrial calcium uniporter (MCU), whose molecular identity has long remained elusive. Since the discovery of the gene encoding the MCU protein two years ago, researchers have awaited the generation of a mouse lacking the MCU. These mice are fully viable and show defects limited to performance of high-energy-demanding exercises. Strikingly, no protection against necrosis is observed following ischaemia-reperfusion in the heart.

Error-free genome segregation depends on the spindle assembly checkpoint (SAC), a signalling network that delays anaphase onset until chromosomes have established proper spindle attachments. Three reports now quantitatively examine the sensitivity and robustness of the SAC response.

In vivo time-lapse imaging and functional tests bring fresh evidence that the morphogen Hedgehog is conveyed to target cells via long filopodia extensions, dubbed cytonemes. This study provides the tools and conceptual framework to understand how cytonemes form and carry morphogens.

The mTOR protein kinase controls anabolic processes as part of mTOR complexes 1 and 2 (mTORC1 and mTORC2). The two complexes are now shown to be involved in a negative feedback regulatory mechanism, in which mTORC1 stimulation inactivates mTORC2 through the inhibitory phosphorylation of the mTORC2 component Sin1.

The role of RNA splicing in the regulation of stem cell properties has remained largely unexplored. The splicing-associated protein SON is now shown to be necessary for embryonic stem cell maintenance, by influencing the splicing of pluripotency regulators.

mTOR is a central controller that integrates many inputs to regulate cell growth and ensure cellular homeostasis. The mTORC1 inhibitor TSC (tuberous sclerosis complex) on the peroxisome is found to inhibit mTORC1 in response to endogenous reactive oxygen species. Thus, mTOR may avoid confounding different inputs by sensing them at different cellular locations.

Cytoplasmic compartments containing misfolded proteins targeted for degradation, named Q-bodies, have been identified. Q-body formation is a dynamic process that actively manages the metastable state of the protein fold through small heat shock proteins and the Hsp70–Hsp90–Hsp110 proteostasis system to promote cellular fitness under both physiological and stress conditions.

During mitosis, kinetochores attach to microtubule plus ends, thus allowing dynamic microtubules to properly segregate chromosomes. How this type of 'end-on' attachment between microtubule plus ends and kinetochores is formed and maintained is unclear. CENP-E, a kinesin-7 family member, is now shown to have a role in associating kinetochores with dynamic microtubule plus ends.

Faithful genome segregation depends on the functions of the eukaryotic centromere, which is characterized by the histone variant CENP-A. Gene replacement in human cells and fission yeast has now been used to show how CENP-A biochemically encodes centromere identity, as well as reveal an unexpected role for CENP-B in centromere function.

The transcription factor p73, a close relative of p53, has complex yet poorly understood roles in tumorigenesis. TAp73, a p73 variant, has now been shown to promote cancer cell proliferation by regulating glucose metabolism to control cellular biosynthetic pathways and antioxidant capacity.