On the cover
A confocal image of an Arabidopsis root after a heat shock treatment. The death of root hairs is evident as assayed by Sytox green nucleic acid stain, which is significantly and specifically prevented by ferroptosis inhibitors. Image © 2017 Distéfano et al.
See page 463.
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People & Ideas
Schuldiner and Zalckvar discuss the identification of a peroxisome–ER tether in human cells by Costello et al. and Hua et al.
Senaratne and Drinnenberg discuss the potential universality of eukaryotic kinetochore proteins based on new work by D’Archivio and Wickstead.
van Vugt previews work by Qu et al. linking the metabolic enzyme PGAM1 to the pool of nucleotides needed for proper DNA repair in cancer cells.
Myers and Payne discuss work by De et al. describing the unique structure of Vps13 and its role in trafficking
Cho, Irianto, and Discher review emerging mechanisms of nuclear mechanosensing and propose through meta-analyses of published data the universality of mechanosensing pathways.
Recent studies show that MAPK pathways perform exquisite spatial and temporal signal processing. This review discusses the mechanisms that process dynamic inputs into graded output responses, the role of positive and negative feedbacks, and feedforward regulation.
Costello et al. identify ACBD5 and VAPB as key components of a peroxisome–ER tether in mammalian cells. Disruption of this tethering complex leads to reduced peroxisomal membrane expansion and increased peroxisomal movement.
mTORC2 integrates extracellular cues with pathways controlling growth and proliferation, but the spatial control of mTORC2 activity is unclear. Using a new reporter, Ebner et al. show that endogenous mTORC2 activity localizes to plasma membrane, mitochondrial, and endosomal pools, which display distinct sensitivity to growth factors.
DGCR8 is essential for mouse early development and microRNA biogenesis. Cirera-Salinas et al. report a new noncanonical function of DGCR8 essential for the exit from pluripotency of mouse embryonic stem cells.
Peroxisomes and the ER exchange lipids for various metabolic and anabolic reactions. In this study, Hua et al. show that the interaction between the ER-resident VAPs with the peroxisomal protein ACBD5 tethers peroxisomes to the ER. This tether is required for the exchange of lipids, including cholesterol, between the two organelles.
Trypanosome outer kinetochore proteins suggest conservation of chromosome segregation machinery across eukaryotes
The kinetochore complex is conserved across many eukaryotes, but the protozoan lineage Kinetoplastida builds kinetochores from components without apparent homology to models. D’Archivio and Wickstead describe a new family of proteins with homology to outer kinetochore proteins Ndc80 and Nuf2 that defines the outer kinetochore of trypanosomes, suggesting that all eukaryotes have divergent versions of a universal kinetochore machine.
Dynein-mediated movement of microtubules is required for chromosome movement; its absence leads to aberrant segregation. Alleva et al. show that FKB-6, a cochaperone of Hsp-90, is required for proper chromosome movement through down-regulation of resting time between movements.
Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells
Phosphoglycerate mutase 1 (PGAM1) regulates metabolism in cancer cells. Qu et al. show that PGAM1 maintains the intracellular dNTP pool, promotes the stability of CTBP-interacting protein, and is required for homologous recombination repair. PGAM1 inhibition sensitizes BRCA1/2-proficient breast cancer to PARP inhibitors.
The Vps13p–Cdc31p complex is directly required for TGN late endosome transport and TGN homotypic fusion
VPS13 proteins are widely conserved in eukaryotes and associated with human neurodegenerative and neurodevelopmental diseases. De et al. describe the lipid specificity and structure of yeast Vps13p, providing insight into its role in both TGN late endosome transport and TGN homotypic fusion.
A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation
The regulation of cargo transport within neurons is not well understood. Neisch et al. use Drosophila genetics to identify a multiprotein STRIPAK complex required for autophagosome and dense core vesicle transport in neurons. PP2A activity within the complex is necessary for transport.
Distéfano et al. show that an iron-dependent, oxidative cell death process with biochemical and morphological similarities to ferroptosis, as described in mammalian cells, has a physiological role in plants, regulating plant cell death in response to heat stress.
The pathophysiological function and induction mechanism of autophagy in neuronal axons have remained unclear. Wakatsuki et al. show that the GSK3B-mediated phosphorylation of MCL1 leads to its UPS-dependent degradation, which induces axonal autophagy and promotes axonal degeneration.
The regenerative capacity of Schwann cells in the PNS underlies functional repair after injury. In this study, Mindos et al. show a new function for the tumor suppressor Merlin and Hippo/YAP signaling in the generation of repair-competent Schwann cells after injury.
A targeted RNAi screen identifies factors affecting diverse stages of receptor-mediated transcytosis
Transcytosis plays an important role in establishing cell polarity and in mediating transport of large cargo across epithelial barriers, but its molecular basis is unclear. Nelms et al. present a new dataset of genes involved in receptor-mediated transcytosis and show that the apical and basolateral recycling and transcytotic pathways are genetically separable.