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.
See page 524.
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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.
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.
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.
Soni Lacefield discusses new findings from Sawyer et al. revealing the developmental regulation of mitochondrial detachment from the cell cortex during meiosis.
Leandro and Houten highlight new work from Zhou et al. exploring the disease relevance and toxicity of lysine metabolites in mitochondria.
Miroshnikova, Hammesfahr, and Wickström illustrate the complex cell biological changes observed in cells of patients with Lamin A/C cardiomyopathies.
Taniguchi et al. review recent advances in stem cell–based models to investigate early human post-implantation development
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.