Issues
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Cover Image
Cover Image
ON THE COVER
A repeated pattern made in Adobe Illustrator of an image from a single Drosophila third instar larval myonucleus (DAPI, blue) surrounded by microtubules (anti-tubulin, white). Image © Rosen et al., 2019.
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People & Ideas
Xiaochen Wang: Building up our understanding of breaking down
Wang studies lysosomal degradation pathways using C. Elegans as a model system.
Spotlights
TPX2 joins 53BP1 to maintain DNA repair and fork stability
Cantor previews work from the Mosammaparast laboratory showing that the mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function.
A mosaic of old and young nucleoporins
Shimi and Kimura preview work from the Hetzer laboratory visualizing nuclear long-lived proteins, histones and nucleoporins, and the pattern of nucleoporin renewal, providing insight into protein longevity in nuclear maintenance and its function.
Dendritic cells mature to resist lamin degradation and herpes virus release
Florence Niedergang introduces work by Turan et al. demonstrating that herpes virus egress from dendritic cells is differentially regulated by kinesin-dependent positioning of lysosomes and autophagic degradation of nuclear lamins.
Detaching the tether: Remodeling mitochondrial localization during meiosis
Soni Lacefield discusses new findings from Sawyer et al. revealing the developmental regulation of mitochondrial detachment from the cell cortex during meiosis.
Saccharopine, a lysine degradation intermediate, is a mitochondrial toxin
Leandro and Houten highlight new work from Zhou et al. exploring the disease relevance and toxicity of lysine metabolites in mitochondria.
Discussion/Inside Look
Cell biology and mechanopathology of laminopathic cardiomyopathies
Miroshnikova, Hammesfahr, and Wickström illustrate the complex cell biological changes observed in cells of patients with Lamin A/C cardiomyopathies.
Reviews
Protein phosphatases in the regulation of mitosis
Nilsson reviews the essential role of phosphoprotein phosphatases in the regulation of controlled dephosphorylation during cell division.
Opening the black box: Stem cell–based modeling of human post-implantation development
Taniguchi et al. review recent advances in stem cell–based models to investigate early human post-implantation development
Reports
Mitotic regulators TPX2 and Aurora A protect DNA forks during replication stress by counteracting 53BP1 function
The TPX2/Aurora A heterodimeric kinase canonically orchestrates mitotic events. Byrum et al. identify two new roles for this complex in regulating DNA double-stranded break repair and the protection of DNA forks during replication stress.
Visualization of long-lived proteins reveals age mosaicism within nuclei of postmitotic cells
Toyama et al. monitor the replacement of long-lived components of nuclear pore complexes (NPCs) and nucleosomes in postmitotic cells. They describe age mosaicism at the level of chromatin organization and find that NPCs are maintained by piecemeal replacement in postmitotic nondividing cells but by entire complex replacement in an ESCRT-dependent manner in nondividing, starved quiescent cells.
Time-resolved ultrastructure of the cortical actin cytoskeleton in dynamic membrane blebs
Chikina et al. show preferential initiation of blebbing at local cytoskeleton weaknesses at filopodial bases when blebbing is induced by Arp2/3 complex inhibition. They also use correlative platinum replica electron microscopy to characterize actin cytoskeleton architecture in blebs at different stages of their expansion–retraction cycle.
Articles
Electron cryotomography analysis of Dam1C/DASH at the kinetochore–spindle interface in situ
Kinetochore subcomplexes have been studied extensively in vitro, but little is known about their structure and interactions with microtubules in cells. Ng et al. combine electron cryotomography of serial cryosections with genetic and pharmacological perturbation to study yeast Dam1C/DASH complexes and the kinetochore–microtubule interface inside cells.
Drosophila kinesin-8 stabilizes the kinetochore–microtubule interaction
Kinesin-8 motor proteins control chromosome alignment in a variety of species, but the specific biochemical activity responsible is unclear. Edzuka and Goshima find that Drosophila kinesin-8 (Klp67A) exhibits both microtubule plus end–stabilizing and –destabilizing activities in vitro. In cells, Klp67A, and likely human kinesin-8 (KIF18A) as well, stabilize the kinetochore–microtubule attachment during mitosis.
Dual regulation of lin28a by Myc is necessary during zebrafish retina regeneration
In zebrafish, the damaged retina can regenerate with the help of Muller glia–derived progenitor cells. Mitra et al. show that Mycb regulates lin28a, a facilitator of regeneration, both as an activator and repressor in selected cells. Further, Mycb in collaboration with Hdac1 represses her4.1, a negative regulator of retina regeneration.
Autophagic degradation of lamins facilitates the nuclear egress of herpes simplex virus type 1
Turan and Grosche et al. show that herpes simplex virus type 1 (HSV-1) infection leads to autophagic degradation of nuclear lamins in immature dendritic cells, facilitating HSV-1 nuclear egress and the formation of infectious progeny virus. In mature dendritic cells, autophagy is inhibited due to elevated KIF1B and KIF2A protein levels.
The Drosophila Ninein homologue Bsg25D cooperates with Ensconsin in myonuclear positioning
Rosen et al. identify a role for the centrosomal protein Bsg25D/Ninein in nuclear positioning and microtubule organization in Drosophila muscle fibers. Genetic, cell biological, and atomic force microscopy analyses demonstrate that complex interactions between Bsg25D and the microtubule-associated protein Ensconsin govern myonuclear positioning in Drosophila.
ENSA and ARPP19 differentially control cell cycle progression and development
The Greatwall kinase substrates ARPP19 and ENSA have been shown to inhibit PP2A-B55 by an identical mechanism. Hached et al. show that, surprisingly, the ARPP19 and ENSA paralogs display specific functions during mouse embryogenesis and differentially control cell cycle progression.
Developmental regulation of an organelle tether coordinates mitochondrial remodeling in meiosis
Organelle tethers stabilize contact sites between organelles, yet cellular architecture is dynamically remodeled during cellular differentiation. Sawyer et al. demonstrate that a conserved CDK-like kinase, Ime2, promotes cellular remodeling through destruction of mitochondria–plasma membrane contact sites in yeast gametogenesis.
The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis
Defective lysine catabolism leads to two types of hyperlysinemia, but the mechanisms are unclear. Zhou et al. reveal that accumulation of saccharopine, an intermediate of lysine catabolism, leads to defective development of Caenorhbditis elegans and mice and that this correlates with disrupted mitochondrial dynamics, damage, and functional loss.
ROMO1 is a constituent of the human presequence translocase required for YME1L protease import
Mitochondria are the powerhouses of eukaryotic cells and rely on protein import from the cytosol. Richter et al. found ROMO1 as a new constituent of the human mitochondrial import machinery linking protein import to quality control and mitochondrial morphology.
Retromer has a selective function in cargo sorting via endosome transport carriers
The molecular actions of retromer in the endolysosomal system remain unclear and controversial. Cui et al. demonstrate the essential role of retromer in the selective incorporation of cargo into a specific type of endosome transport carrier and the maintenance of lysosomal function.
Detyrosinated microtubules spatially constrain lysosomes facilitating lysosome–autophagosome fusion
Detyrosinated microtubules constitute a minor subpopulation of microtubules in epithelial cells. Lysosomes are specifically enriched on detyrosinated microtubules through a kinesin-1–dependent mechanism. This spatial constraining of lysosomes to a subset of microtubules enables them to efficiently encounter and fuse with autophagosomes to initiate autophagy.
A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor
Liu et al. describe a previously unrecognized cellular complex (∼5 MD) containing β- and γ-secretases that generates a full array of Aβ peptides with physiological Aβ42/40 ratios by sequential cleavages of holo-APP. Such coordinated substrate processing also occurs with the α- and γ-secretases in the RIP mechanism.
BAR scaffolds drive membrane fission by crowding disordered domains
Cylindrical protein scaffolds are thought to stabilize membrane tubules, preventing membrane fission. In contrast, Snead et al. find that when scaffold proteins assemble, bulky disordered domains within them become acutely concentrated, generating steric pressure that destabilizes tubules, driving fission.
Single event visualization of unconventional secretion of FGF2
FGF2 is a cell survival factor secreted by unconventional means. Dimou et al. visualize individual FGF2 translocation events at the plasma membrane by live cell TIRF microscopy, providing insight into the kinetics and the mechanism of this process.
Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS
In this study, Niu et al. suggest a role for pericytes in cocaine-mediated neuroinflammation. Exposure of pericytes to cocaine results in dose- and time-dependent release of CXCL10, which in turn leads to a concomitant induction of monocyte transmigration mediated by the σ-1R–Src–PDGFR-β–NF-κB axis.