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    ON THE COVER
    Transmission electron micrograph showing endoplasmic reticulum (ER) wrapping around lipid droplets (LDs) of U2OS cells overexpressing Snx14EGFP-APEX2, which stabilizes ER–LD contacts. Image © Datta et al., 2019. See page 1335.

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ISSN 0021-9525
EISSN 1540-8140

People Ideas

Fritz-Laylin studies the evolution of complex protein networks associated with cell movement.

Spotlights

McMurray highlights work from Cannon and Gladfelter that reveals how septins sense micron-scale membrane curvature.

Orr and Maiato discuss work from the Stumpff laboratory addressing the role of chromosome congression in mitotic fidelity and genomic stability.

Nguyen and Olzmann highlight new findings from the Henne laboratory that provide insights into the functions of lipid droplet tethers.

Nair and Wirtz preview work from Mason et al. showing that YAP/TAZ signaling regulates a transcriptional feedback pathway necessary for migration persistence.

Discussion/Inside Look

Park and Woo outline the cellular events leading to failure of the insulin-producing β cells in type 2 diabetes.

Reviews

Rickman and Smogorzewska discuss recent studies that detail the cellular mechanisms protecting genome stability at sites of stalled DNA replication.

Reports

CDK1-CCNB1 plays a well-established role in promoting mitosis. Alfonso-Pérez et al. now show that CDK1-CCNB1 forms a complex with the spindle checkpoint protein MAD1 at unattached kinetochores that directly promotes spindle checkpoint signaling.

Bae et al. show that degradation of the mRNA encoding the adaptor Blos1 leads to the repositioning of late endosomes/lysosomes to the microtubule-organizing center in response to ER stress. This repositioning enhances cell survival during stress by promoting the clearance of protein aggregates.

The basis of curvature sensing by the septin cytoskeleton is unknown. Cannon et al. now identify a conserved amphipathic helix that is necessary for recruitment of septins to sites of micrometer-scale curvature in vitro and in vivo.

Actin assembly and type I myosins are both required for clathrin-mediated endocytosis. Here Pedersen and Drubin show that type I myosins anchor actin assembly factors to the plasma membrane at sites of clathrin-mediated endocytosis, facilitating force generation by actin assembly.

Articles

The alignment of chromosomes at the center of the mitotic spindle is a highly conserved step during cell division. Fonseca et al. find that mammalian cells with alignment defects due to lack of KIF18A function display interchromosomal compaction problems during anaphase and form abnormal nuclei after cell division.

Seibert et al. identify a new phosphorylation event of histone H2B at serine 6 during mitosis with CDK1 and PP1 as writers and erasers of this modification. This phosphorylation contributes to chromatin dislocation of the histone chaperone SET during mitosis and is required for mitotic chromosome segregation.

Hayward et al. show that CDK1-CCNB1 and PP2A-B55 limit spindle checkpoint signaling to a tightly defined window during mitosis. CDK1-CCNB1 promotes MPS1 localization to unattached kinetochores and thus creates a checkpoint-permissive state that is terminated by PP2A-B55 upon mitotic exit.

In this study, Franco and Carmena uncover a function for Eph signaling as a novel extrinsic mechanism controlling mitotic spindle alignment in Drosophila neuroepithelial cells through aPKC activity–dependent myosin II regulation. Additionally, Eph loss leads to a Rho signaling–dependent activation of the PI3K–Akt1 pathway, enhancing cell proliferation within this neuroepithelium.

Kinesin-binding protein (KBP) is identified as a regulator of the kinesins KIF18A and KIF15 during mitosis. KBP buffers the activity of these motors to control chromosome alignment and spindle integrity in metaphase and prevent lagging chromosomes in anaphase.

Bass and Cortez use comparative quantitative mass spectrometry analyses of cells lacking either ATR activator, ETAA1 or TOPBP1. They identify a role for ETAA1 and ATR activation in the regulation of chromosome alignment and segregation in mitosis through Aurora B activity.

Adriaans et al. provide evidence for the existence of two molecular pathways that can initiate cytokinesis in human cells: one depending on PLK1 and originating at the spindle midzone and the other depending on Aurora B activity at the equatorial cortex.

Cyclins control the switch-like cell cycle transitions that orchestrate orderly duplication and segregation of genomes. Karasu et al. delineate an essential function for mouse cyclin B3 for anaphase onset in the first meiotic division of oocytes.

Oscillations in p53 expression are critical for regulating the cellular response to DNA damage. Hanson et al. show that the relationship between p53 pulse frequency and target mRNA and protein decay rates regulates stress response pathway dynamics and function.

Hooikaas et al. show that mammalian MAP7 family proteins act redundantly to activate the kinesin-1 motor protein. Using experiments in cells and in vitro reconstitution assays, they demonstrate that MAP7 proteins promote microtubule recruitment and processivity of kinesin-1 by transiently associating with the stalk region of the motor.

Excess fatty acids are toxic to cells but can be sequestered as triacylglycerides in lipid droplets. Hariri et al. show that the tethering protein Mdm1 spatially regulates this process at the junction between the endoplasmic reticulum and the yeast vacuole. These findings suggest that Mdm1 can drive spatially defined lipid droplet production to maintain cell homeostasis and protect against lipotoxicity.

Free fatty acids are toxic, but are stored in lipid droplets (LDs) that bud from the ER. Datta et al. show that cerebellar ataxia–linked protein Snx14 localizes to ER–droplet contacts and promotes LD growth. This implicates Snx14 in LD homeostasis which, when perturbed, contributes to disease.

CoQ lipids are built at the mitochondrial inner membrane by a multicomponent pathway. Subramanian et al. reveal that CoQ pathway components assemble via CoQ intermediates into domains at ER–mitochondria contacts, suggesting that CoQ domains function as metabolons that facilitate processive CoQ production and distribution.

The importance of transcription during cell motility is controversial. Mason et al. show that YAP/TAZ-mediated transcription is required to limit cytoskeletal tension generation and permit persistent cell motility. This pathway is defined as a negative feedback loop whereby Rho-ROCK-myosin activate YAP and TAZ, which limit myosin activation through NUAK2 expression.

The Wave complex promotes Arp2/3-mediated actin polymerization. Cohen et al. show that Wave complex activity regulates epidermal shape and growth. Without Wave complex activity, F-actin content is down-regulated and ectopic activity of the Wnt/β-catenin–SOX9 pathway is triggered. This activity induces epidermal hyperproliferation and disrupts tissue architecture.

Tools

Cell wall porosity of fungi and plants could not be determined in vivo previously. Application of a novel method links dynamic changes in wall porosity to stress-induced cell elongation in plant roots and uptake of antifungal drugs in yeast cells.

Corrections

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