ON THE COVER
A tissue sample of Barrett’s esophagus dysplasia is shown stained with pericentrin (green) and glutamylated tubulin (red) to identify bona-fide centrosomes. DNA is shown in blue.
Image © Lopes et al., 2018
See page 2353.
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People & Ideas
Erika Pearce: Fitting metabolism and immunity together, to a T
Pearce investigates how metabolism is tailored to immune cell function.
Between sisters: Watching replication-associated recombinational DNA repair
Lovett previews work from Amarh et al. describing the dynamics of RecA-mediated repair at replication-dependent breaks.
Condensins under the microscope
Maeshima et al. preview work from the Walther et al. imaging Condensin behavior and describing its stoichiometry in mitosis to model chromosome condensation.
A transcription factor primes the condensin pump
Gerton introduces new work from Schiklenk et al. identifying the Zas1 transcription factor as a key regulator of chromosome condensation.
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen reviews how cellular metabolism responds acutely to the intense energy requirements of neurons when they are stimulated.
Metabolic regulation of chromatin modifications and gene expression
Schvartzman et al. review how alterations in the levels of specific metabolites in mammalian cells result in chromatin modifications that influence gene expression.
Modulation of the secretory pathway by amino-acid starvation
van Leeuwen et al. discuss how the cellular secretory pathway adapts and contributes to stress-induced pathways during nutrient starvation.
The cell biology of systemic insulin function
Tokarz et al. review the cell biology of insulin physiology throughout the body, from synthesis to the delivery, action, and final degradation of insulin.
Glutathione metabolism in cancer progression and treatment resistance
Bansal and Simon discuss strategies to block glutathione synthesis and utilization pathways to inhibit tumor propagation and treatment resistance.
Dynamics of RecA-mediated repair of replication-dependent DNA breaks
Spontaneous DNA double-strand breaks form during DNA replication and are largely repaired by recombination with a sister chromosome. Using live-cell fluorescence imaging, Amarh et al. show that repair of a replication-dependent break is rapid, localized, and involves a transient RecA focus.
A quantitative map of human Condensins provides new insights into mitotic chromosome architecture
Walther et al. systematically fluorescently tag endogenous Condensin subunits and map their abundance, physical spacing, and mitotic dynamics by fluorescence correlation spectroscopy–calibrated live-cell imaging and superresolution microscopy. They propose a three-step hierarchical loop model of mitotic chromosome compaction.
Xpo7 is a broad-spectrum exportin and a nuclear import receptor
Aksu et al. explore the vast cargo spectrum of exportin7/Xpo7 and present anti-Xpo7 nanobodies that acutely inhibit Xpo7’s transport cycles in living cells. Their expression selectively blocks nuclear enrichment of import cargoes as well as nuclear exclusion of export cargoes, establishing Xpo7 as a novel bidirectional nuclear transport receptor.
Nuclear transport adapts to varying heat stress in a multistep mechanism
Using a newly developed temperature shift assay, Ogawa and Imamoto find that nuclear transport pathways have different sensitivities to rising temperatures. The data suggest that the thermosensitivity of importin α1 enables a multistep shutdown of Ran-dependent transport according to the degree of heat stress.
Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis
Lopes et al. examine centrosomes in human samples progressing from premalignant to metastatic lesions from patients with Barrett’s esophagus. They find that centrosome amplification can occur before transformation during human tumorigenesis, being repressed by p53, suggesting that centrosome amplification contributes to tumor initiation before p53 mutation.
Centrobin is essential for C-tubule assembly and flagellum development in Drosophila melanogaster spermatogenesis
This work shows that Centrobin (CNB) mutant males assemble aberrant basal bodies and do not produce functional sperm. It also shows that CNB can act as a positive or negative regulator of ciliogenesis in a cell type–dependent manner.
Adherens junctions influence tight junction formation via changes in membrane lipid composition
How adherens junctions (AJs) influence tight junction (TJ) formation in epithelial cells is unclear. Shigetomi et al. show that loss of AJs affects plasma membrane (PM) lipid composition and that cholesterol addition in α-catenin–knockouts rescues TJ formation. In total, their data suggest that AJs affect TJ formation by controlling PM lipid levels.
Control of mitotic chromosome condensation by the fission yeast transcription factor Zas1
How chromosomes compact into rod-shaped structures is a longstanding unresolved question of cell biology. Schiklenk et al. identify the transcription factor Zas1 as a central regulator of mitotic chromosome condensation in fission yeast and show that it uses a conserved transactivation domain–based mechanism to control gene expression.
Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
Kinesin-8 Kif18b shortens astral microtubules in mitosis. Combining cell biology and biochemical reconstitution, McHugh et al. show that Kif18b walks and accumulates to microtubule plus ends in a phosphospecific manner to regulate astral microtubule dynamics and center the mitotic spindle.
Mechanism of how augmin directly targets the γ-tubulin ring complex to microtubules
Microtubules can nucleate new microtubules from preexisting microtubules, which is important for spindle assembly and requires the protein complex augmin. Song et al. now show that augmin functions as a direct bridge between the preexisting microtubule and the g-tubulin ring nucleation complex forming the base of the new microtubule.
Prolonged cyclin-dependent kinase inhibition results in septin perturbations during return to growth and mitosis
By investigating how yeast cells coordinate polarity and division in a special type of cell division called return to growth, Gihana et al. discover that although checkpoints are normally beneficial, prolonged activation of the morphogenesis checkpoint is instead detrimental to the cell.
The budding yeast RSC complex maintains ploidy by promoting spindle pole body insertion
Sing et al. characterize an unanticipated role for the Saccharomyces cerevisiae RSC complex in ploidy maintenance. They show that RSC promotes the distribution of Nbp1 and Ndc1 to the spindle pole body (SPB) to facilitate SPB maturation and accurate chromosome segregation.
Uncoordinated centrosome cycle underlies the instability of non-diploid somatic cells in mammals
Mammalian somatic cells are more stable as diploids, but the mechanisms underlying this stability are unclear. Yaguchi et al. show that changes in centriole licensing compromise the control of centrosome number in haploid or tetraploid human cells, suggesting that the ploidy-dependent control of the centrosome cycle explains the instability of non-diploid karyotypes.
Centrosome amplification disrupts renal development and causes cystogenesis
Supernumerary centrosomes are commonly observed in cystic kidneys, but whether they are a cause or consequence of cystogenesis is unknown. Dionne et al. demonstrate that centrosome amplification disrupts renal development and is sufficient to induce cystogenesis in vivo.
Hierarchical recruitment of ribosomal proteins and assembly factors remodels nucleolar pre-60S ribosomes
Ribosome biogenesis involves numerous pre-rRNA processing events to remove internal and external transcribed spacer sequences, ultimately yielding three mature rRNAs. Biedka et al. show that ribosomal proteins and assembly factors remodel several neighborhoods, including two 60S ribosomal subunit functional centers, during removal of the ITS2 spacer RNA.
The universally conserved GTPase HflX is an RNA helicase that restores heat-damaged Escherichia coli ribosomes
HflX, which was recently identified as a heat shock protein, is a putative GTPase. HflX also has ATPase activity, but the role of this is unknown. Dey at al. now reveal that HflX has ATP-dependent RNA helicase activity that is instrumental in recovering heat-inactivated 50S rRNA in Escherichia coli.
Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts
Neuronal polarity relies on the axon- or dendrite-specific localization of cargo by molecular motors such as kinesin-1. This study shows how autoinhibition regulates both kinesin-1 activity and localization to keep dendritic Golgi outposts from entering axons.
HRS–WASH axis governs actin-mediated endosomal recycling and cell invasion
ESCRT-0 component HRS and actin polymerization factor WASH reside in adjacent endosomal domains. MacDonald et al. show that HRS controls WASH localization and recycling of WASH-dependent transmembrane cargo. Cargo binding to endosomal actin thus acts as sorting signal to oppose ubiquitin-mediated degradation.
PI(4,5)P2 determines the threshold of mechanical force–induced B cell activation
Antigens deliver mechanical forces to B cell receptors (BCRs) to initiate B cell activation. Using mechanical force biosensors, Wan et al. show that the enrichment of PI(4,5)P2 within the IgG-BCR membrane microdomain determines the threshold of mechanical force–induced B cell activation.
Ciliary dynein motor preassembly is regulated by Wdr92 in association with HSP90 co-chaperone, R2TP
Wdr92 is associated with the multifunctional cochaperone, R2TP, but its function is unknown. In this study, the authors show that Drosophila Wdr92 is exclusively required for preassembly of ciliary dynein motor complexes, which are confined to sensory neuron ciliary dendrites and sperm flagella. Wdr92 is proposed to direct R2TP/HSP90 to dynein chain clients to chaperone cytoplasmic preassembly.