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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. - PDF Icon PDF LinkTable of Contents
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People & Ideas
Efraín E. Rivera-Serrano: Personal training for scientists
Rivera-Serrano investigates the host cell genes that support viral infection.
Spotlight
A precision RNA degradation machinery shapes stem cell development
Pereira and Arraiano preview work from the Wolin laboratory that uncovers an important regulatory role for the RNA exosome in stem cell development.
Spastin joins LDs and peroxisomes in the interorganelle contact ballet
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.
Neurexin nanoclusters: A novel structure at presynaptic terminals
Kawaguchi and Gotoh highlight new work from Trotter et al. visualizing dynamic nanoclusters of neurexins in presynaptic terminals.
Review
Assembling nuclear domains: Lessons from DNA repair
Schrank and Gautier discuss the generation and function of nuclear domains during DNA repair with a special focus on nuclear actin polymerization.
Beyond proteases: Basement membrane mechanics and cancer invasion
Chang and Chaudhuri discuss basement membrane mechanics and how cells use both proteolytic and physical mechanisms to invade basement membranes during cancer progression.
Report
LTK is an ER-resident receptor tyrosine kinase that regulates secretion
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.
Filamin A mediates isotropic distribution of applied force across the actin network
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
Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes
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.
SET binding to Sgo1 inhibits Sgo1–cohesin interactions and promotes chromosome segregation
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.
High-resolution imaging reveals how the spindle midzone impacts chromosome movement
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.
Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle
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.
The RNA exosome nuclease complex regulates human embryonic stem cell differentiation
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.
Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III
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.
Higher-order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes
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.
The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation
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 inCaenorhabditis elegans embryos and autophagic lysosome reformation in adult animals.
Maize defective kernel5 is a bacterial TamB homologue required for chloroplast envelope biogenesis
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.
Developmentally regulated GTP-binding protein 1 modulates ciliogenesis via an interaction with Dishevelled
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.
Synaptic neurexin-1 assembles into dynamically regulated active zone nanoclusters
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.
SGEF forms a complex with Scribble and Dlg1 and regulates epithelial junctions and contractility
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.
Microtubules promote intercellular contractile force transmission during tissue folding
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.
Cross-linker–mediated regulation of actin network organization controls tissue morphogenesis
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.
Yorkie controls tube length and apical barrier integrity during airway development
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
Quantitative glycoproteomics reveals new classes of STT3A- and STT3B-dependent N-glycosylation sites
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.
High-throughput ultrastructure screening using electron microscopy and fluorescent barcoding
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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