ON THE COVER
The cover shows a 3D iPALM image of a 3T3 fibroblast expressing mEOS2-EVL and stained with Alexa Fluor 647 phalloidin. Depth color coding was applied using a spectrum of colors ranging from warm (bottom of the cell) to cool (top of the cell). Image © Puleo et al., 2019. See https://doi.org/10.1083/jcb.201902101.
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People & Ideas
González Besteiro and Gottifredi discuss work from the Mailand laboratory shedding light on ETAA1’s role in S phase and work from the Cortez laboratory reporting a role for ETAA1 in mitosis.
Kumsta and Hansen highlight new findings from Zhang and Zhang exploring how local cellular stress triggers autophagy in distant tissues.
Kahanovitch and Olsen preview work from Li et al. that reveals a role for SIK3-HDAC4-Mef2 signaling in the regulation of glial cell K+ and water buffering and neuronal excitability.
Lemmens and Lindqvist discuss how DNA replication and mitosis are coordinated and propose a cell cycle model controlled by brakes.
Peterman and Prekeris review abscission and discuss the diverse roles for the postmitotic midbody in regulating polarity, tumorigenesis, and stemness.
Abad et al. report that the chromosomal passenger complex (CPC), an essential regulator of error-free chromosome segregation, is targeted to chromosomes via Borealin-mediated direct interaction with nucleosomes. This is critical for subsequent histone modification–dependent centromere enrichment and function of the CPC during metaphase.
Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation
Roy et al. highlight a harmful cross-talk that can arise between spindle assembly checkpoint silencing and chromosome biorientation due to the involvement of protein phosphatase 1 in both the processes.
Achuthankutty et al. show that the recently identified ATR kinase activator ETAA1 has an important role in protecting against chromosomal instability arising from incompletely replicated DNA, driven by cell cycle– and replication stress–regulated, phosphorylation-dependent control of its ATR-activating domain.
The retromer complex is responsible for the endosomal sorting of numerous nutrient transporters. In this study, Curnock et al. show that in response to nutrient deprivation, retromer is transcriptionally regulated by TFEB and acts to support adaptive nutrient acquisition through endosomal recycling of the glutamine transporter, SNAT2 (SLC38A2).
Baumgart et al. measure the amount of dimeric and polymeric tubulin at mitotic centrosomes in C. elegans by light and electron microscopy. Centrosomes concentrate soluble tubulin tenfold over the cytoplasm, suggesting that centrosomal microtubule nucleation may be driven in part by concentrating tubulin.
Genetic studies revealed that Abl family kinases interact functionally with microtubules, but the mechanism by which Abl kinases regulate microtubules remains unclear. Hu et al. provide the first evidence that the Abl family kinase Abl2 directly binds microtubules to regulate microtubule dynamics.
Autophagy can be triggered at the organismal level as a systemic response to protect organs during stressful conditions, but the underlying mechanisms are poorly understood. Zhang et al. identify a TGFβ-like molecule, DAF-7, that acts as a systemic factor and activates a canonical TGFβ signaling pathway in distant tissues to induce autophagy.
Mitochondrial stress causes neuronal dysfunction via an ATF4-dependent increase in L-2-hydroxyglutarate
Hunt et al. show that mitochondrial stress in Drosophila neurons activates ATF4 expression, resulting in increased L-2-hydroxyglutarate (L-2-HG) levels. Reducing L-2-HG levels improves neuronal activity, demonstrating that increased L-2-HG contributes to neuronal dysfunction.
Glia regulate ion and water homeostasis to regulate neuronal excitability. Li et al. describe a SIK3/HDAC4/Mef2 signaling axis in Drosophila that controls the glial capacity to buffer potassium and water via expression of key transport molecules. Disruption of this program causes nerve edema, neuronal hyperexcitability, and seizure.
Wang et al. identify Rab7 as a novel regulator of primary cilia disassembly. Their findings demonstrate that Rab7 localization to primary cilia is required for intraciliary F-actin polymerization, which is indispensable for the regulation of cilia ectocytosis and disassembly.
Kinetochore localization of CENP-C, which is a key and conserved kinetochore component, is regulated during cell cycle progression. Watanabe et al. demonstrate that CDK1-mediated CENP-C phosphorylation regulates mitotic kinetochore localization via binding of CENP-C to the CENP-A nucleosome.
How is nuclear size regulated relative to cell size? Using microfluidic encapsulation of Xenopus laevis embryo extracts, biochemical fractionation, and in vivo experiments, Chen et al. demonstrate that reductions in cytoplasmic volume and limiting components, including the histone chaperone nucleoplasmin, contribute to developmental nuclear size scaling.
Patteson et al. demonstrate that vimentin intermediate filaments in mesenchymal cells form a cage-like filamentous network around the nucleus that protects the cell against extreme nucleus deformations, rupture, and DNA damage during migration in constricted 3D spaces.
Confinement hinders motility by inducing RhoA-mediated nuclear influx, volume expansion, and blebbing
The nucleus is a significant obstacle that impedes migration of cells through confining microenvironments. Mistriotis et al. propose a conceptual model in which confinement-induced RhoA/myosin-II activation promotes nuclear volume expansion, nuclear envelope blebbing, and rupture by triggering passive nuclear influx from the cell posterior, ultimately leading to reduced cell motility.
Bondaz et al. show that in C. elegans embryos, the microtubule depolymerase KLP-7/MCAK is required for efficient centrosome separation in the somatic AB cell, but not the germline P1 cell. This difference in spindle assembly depends on cell polarity via the mitotic kinase PLK1.
Stress granules and paraspeckles are prototypical RNP granules localized in the cytoplasm and nucleus, respectively. An et al. show that despite spatial separation, these two granules are interconnected, and stress granules act as key regulators of stress-induced paraspeckle hyperassembly.
Disease-associated mutations in Niemann-Pick type C1 alter ER calcium signaling and neuronal plasticity
Tiscione et al. report a molecular mechanism that links lysosomal cholesterol export with the regulation of key intracellular Ca2+ signaling pathways to influence synaptic architecture in health and neurodegenerative NPC1 disease.
Membrane association but not identity is required for LRRK2 activation and phosphorylation of Rab GTPases
Parkinson’s disease–associated LRRK2 kinase is activated on the Golgi by Rab29 but phosphorylates Rab10 there and on other compartments. This study shows that phosphorylation is restricted to membrane surfaces but need not take place on the Golgi.
Two S. pombe septation phases differ in ingression rate, septum structure, and response to F-actin loss
Ramos et al. establish that fission yeast septation proceeds in two phases. Initially, the septum is immature and, upon F-actin depolymerization, loses the Bgs1 glucan synthase and fails to ingress. During a second phase, the mature septum can maintain Bgs1 and ingression without F-actin, and ingression becomes Cdc42 and exocyst dependent.
The cell cortex is populated by various proteins, but it is unclear how they interact to change cell shape. Jiang and Harris find that the kinase Par-1 is required for Diaphanous-based actin bundles, and that these bundles intersperse with separately induced Arp2/3 networks to form an actin cap that grows into a metaphase compartment of the syncytial Drosophila embryo.
Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions
Puleo et al. identify the Ena/VASP protein EVL as a crucial actin polymerization factor at focal adhesions, which regulates focal adhesion maturation and mechanosensing. Interestingly, they show that EVL promotes mechanically directed motility and durotactic invasion yet suppresses chemotactic response.
Fu et al. use a WT versus mutant comparison and cryo-electron tomography of Chlamydomonas flagella to identify central apparatus (CA) subunits and visualize their location in the native 3D CA structure. This study provides a better understanding of the CA and how it regulates ciliary motility.