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    ON THE COVER
    High-voltage electron microscopy image of an example of the frequent budding and tubulation of lysosomes in wild-type C. elegans hypodermis that is not observed on enlarged autolysosomes of cells lacking the amino acid transporter SLC-36.1 and PtdIns3P 5-kinase. Image © Gan et al., 2019. See page 2619.

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ISSN 0021-9525
EISSN 1540-8140
In this Issue

People & Ideas

Rivera-Serrano investigates the host cell genes that support viral infection.

Spotlight

Pereira and Arraiano preview work from the Wolin laboratory that uncovers an important regulatory role for the RNA exosome in stem cell development.

W.M. Henne previews work from Chang et al. that demonstrates a role for Spastin in tethering lipid droplets to peroxisomes to facilitate fatty acid exchange.

Kawaguchi and Gotoh highlight new work from Trotter et al. visualizing dynamic nanoclusters of neurexins in presynaptic terminals.

Review

Schrank and Gautier discuss the generation and function of nuclear domains during DNA repair with a special focus on nuclear actin polymerization.

Chang and Chaudhuri discuss basement membrane mechanics and how cells use both proteolytic and physical mechanisms to invade basement membranes during cancer progression.

Report

The endoplasmic reticulum (ER) is a major regulator of cellular proteostasis. However, only little is known about signaling molecules resident to this organelle. Centonze et al. identify LTK as the first ER-resident receptor tyrosine kinase and show that it stimulates secretory trafficking out of the ER.

In this work, Kumar et al. use their previously developed talin tension sensor to study the immediate response of cells to uniaxial stretch. Tension measurements together with high-resolution electron microscopy reveal a novel role for the actin cross-linking protein filamin A in mediating tensional symmetry within the F-actin network.

Article

Potapova et al. use superresolution microscopy to describe linkages between ribosomal DNA on heterologous human chromosomes whose formation depends on the transcription factor UBF and topoisomerase II. Linkages persist in the absence of cohesion but require topoisomerase II for resolution.

Sgo1 is essential for centromeric cohesion protection; however, how it is disabled at anaphase onset is not quite understood. Qu et al. report that SET inhibits Sgo1–cohesin interactions by binding Sgo1 during mitosis, thus promoting centromeric cohesion resolution and timely chromosome segregation.

Microtubule bundles in the spindle midzone have been reported to either promote or hinder chromosome movement. Pamula et al. examine the assembly dynamics of midzone microtubule bundles during anaphase and how chromosome segregation is impacted by aberrant bundle assembly.

Xia et al. show that constricted migration causes DNA damage and a cell cycle block that is rescued by antioxidant plus myosin II inhibition or overexpressed repair factors. Cell cycle progression exhibits a threshold in the mechanically induced DNA damage.

This work shows that the exosome modulates the levels of LINE-1 retrotransposons and specific miRNAs, lncRNAs, and mRNAs that encode developmental regulators or affect their expression. The exosome restrains stem cell differentiation in part by degrading transcripts encoding FOXH1, a transcription factor crucial for mesendoderm formation.

Lipid droplets (LDs) and peroxisomes form a functional alliance to maintain lipid and energy homeostasis. Chang et al. provide mechanistic insights by describing a tethering complex that comprises LD-localized M1 Spastin and peroxisomal ABCD1 at LD–peroxisome contact sites and supports fatty acid trafficking.

Endosomal maturation and distribution, driven by membrane remodeling, are critical for receptor traffic and signaling. Using both in vitro and in vivo approaches, Wang et al. reveal an unexpected coiled-coil–mediated membrane remodeling activity of SNX16 that controls neuronal endosomal tubulation, distribution, and receptor traffic.

How lysosomes reform following phagolysosomal digestion of apoptotic cells is poorly understood. Gan et al. reveal that the amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocygtic lysosome reformation in Caenorhabditis elegans embryos and autophagic lysosome reformation in adult animals.

Zhang et al. show that the maize dek5 locus is required for chloroplast envelope biogenesis and encodes a TamB-like protein. Bacterial TamB proteins facilitate insertion of β-barrel outer membrane proteins, indicating plastids have a conserved mechanism for envelope membrane biogenesis.

Our study reveals Drg1 as a new binding partner of Dishevelled. The Drg1–Dishevelled association regulates Daam1 and RhoA interactions and activity, leading to polymerization and stability of the actin cytoskeleton, a process that is essential for proper multiciliation.

Using super-resolution microscopy, Trotter et al. illuminate an unexpected nanoscale organization of excitatory synapses in which neurexins are assembled in the presynaptic active zone into dynamic nanoclusters that are regulated by ADAM10-mediated ectodomain cleavage.

Awadia et al. show that SGEF, a RhoG-specific GEF, forms a ternary complex with two members of the Scribble polarity complex, Scribble and Dlg1, and regulates junction formation, apical contractility, E-cadherin stability, and lumen formation in epithelial cells.

During morphogenesis, how intercellular contractile force transmission is maintained in the face of tension is not well understood. Ko et al. describe polarized, noncentrosomal microtubules that promote the attachment of actomyosin to cell junctions for proper tissue-wide force integration.

Spatio-temporal organization of actomyosin contraction during epithelial morphogenesis in Drosophila is regulated by the developmental modulation of actin cross-linking through induction of Bottleneck. Bottleneck protein restrains contractility by promoting actin bundling, functioning in a similar way to Filamin and in an opposite way to Fimbrin.

Skouloudaki et al. identify an alternative role of the transcriptional coactivator Yorkie (Yki) in controlling water impermeability and tube size of developing Drosophila airways. Tracheal impermeability is triggered by Yki-mediated transcriptional regulation of δ-aminolevulinate synthase (Alas), whereas tube elongation is controlled by binding of Yki to the actin-severing factor Twinstar.

Tools

Cherepanova et al. provide quantitative glycoproteomic analyses of human cells that lack either the STT3A or STT3B oligosaccharyltransferase (OST) complex, revealing new classes of STT3A- and STT3B-dependent glycosylation sites and indicating how cooperation between the OST complexes maximizes acceptor site occupancy in cellular glycoproteins.

Bykov et al. describe a method called “MultiCLEM” to screen ultrastructural phenotypes by high-throughput electron microscopy (EM). The method uses combinations of fluorophores as barcodes to identify cells. It is applied to study multivesicular bodies, mitochondria, and peroxisomes.

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