Issues
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Cover Image
Cover Image
ON THE COVER
This image depicts collective breast cancer cell invasion by a 4T1 mammary tumor 4 d after implantation into the mouse mammary fat pad. All breast cancer cells express H2BmCherry (yellow), and 30% of the cells express LifeAct-eGFP (cyan) for visualizing the actin cytoskeleton. Blood vessels and phagocytes are visualized by dextran-Alexa Fluor 750 (magenta) and collagen fi brils by second harmonic generation (gray). Image © Khalil et al., 2020 https://doi.org/10.1083/jcb.201911120 - PDF Icon PDF LinkTable of Contents
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Spotlights
Nesprin-2G tension fine-tunes Wnt/β-catenin signaling
Gottardi and Luxton preview work from the Borghi laboratory implicating LINC complex proteins as mechanotransducers that fine-tune Wnt/β-catenin signaling during epithelial–mesenchymal transition.
Hands and feet: Closer than you think in epithelial migration
Gupta and Yap preview work by Ozawa and colleagues that elucidates new roles for adherens junctions and cryptic lamellipodia in the collective migration of epithelial cells.
Inflammasomes: Exosomal miRNAs loaded for action
Matikainen et al. preview work from Wozniak et al. that reveals that inflammasomes mediate sequence-specific miRNA loading into exosomes.
Perspectives
Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality
Mast et al. highlight common antiviral strategies and propose exploiting the well-established concept of synthetic lethality as an approach to combat viral infections.
Review
Stable inheritance of CENP-A chromatin: Inner strength versus dynamic control
Centromeres, loci driving chromosome segregation, are marked epigenetically by H3 variant CENP-A. In this review, Mitra et al. discuss the mechanisms of faithful CENP-A inheritance.
Reports
The Pex3–Inp1 complex tethers yeast peroxisomes to the plasma membrane
Organelle inheritance in yeast is a balance between two opposing processes, retention and inheritance. Hulmes et al. propose a new model for peroxisome retention involving contact with the plasma membrane and identify the plasma membrane–peroxisome tether responsible.
Peroxisome retention involves Inp1-dependent peroxisome–plasma membrane contact sites in yeast
In the yeast Hansenula polymorpha, Krikken et al. find that Inp1 tethers peroxisomes to the plasma membrane for organelle retention. The C terminus of Inp1 associates with peroxisomes, while the N terminus, which contains a PH-like domain, is important for plasma membrane binding.
Wnts regulate planar cell polarity via heterotrimeric G protein and PI3K signaling
The planar cell polarity (PCP) pathway is essential for tissue morphogenesis. However, the roles of Wnt ligands in the mammalian PCP pathway remain poorly understood. This study identifies a Wnt/heterotrimeric G protein/PI3K pathway that regulates cell-intrinsic and tissue-level PCP in the mouse cochlea.
The LTB4–BLT1 axis regulates actomyosin and β2-integrin dynamics during neutrophil extravasation
Neutrophils arrest and extravasate from the blood vessels in response to infection and injury. Using intravital subcellular microscopy, Subramanian et al. identify a role for extracellular vesicle–based autocrine/paracrine LTB4/BLT1 signaling in promoting the rearrangement of the actomyosin cytoskeleton and β2-integrin during neutrophil extravasation in live animals.
Notch2 complements Notch1 to mediate inductive signaling that initiates early T cell development
Notch1 has an indispensable role in initiating the T lineage program from progenitors in the thymus. This study defines stage-specific regulation of Notch target genes and shows that Notch2 also amplifies inductive and lineage-restrictive Notch signals in early T cell development.
Articles
NUCKS1 promotes RAD54 activity in homologous recombination DNA repair
Maranon et al. have identified the NUCKS1 protein as a new regulator of the spatiotemporal events in homologous recombination DNA repair. NUCKS1 prevents RAD54–RAD51AP1 association during RAD51 filament formation and synergizes with RAD54 activity in displacement loop formation.
Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging
Here, we show that physiological aging in mice leads to degenerative and fibrotic-like pathologies in the lung and that telomerase gene therapy prevents the onset of these pathologies. Our findings highlight telomerase activation as a potential therapeutic strategy for lung degenerative pathologies associated with aging.
Nesprins are mechanotransducers that discriminate epithelial–mesenchymal transition programs
Déjardin et al. show how nesprin recruits α-catenin to the nuclear envelope in a tension-dependent manner to fine-tune β-catenin transcriptional activity as a function of the epithelial–mesenchymal transition program.
FIT2 is an acyl–coenzyme A diphosphatase crucial for endoplasmic reticulum homeostasis
FIT2 is a protein important for ER lipid metabolism and lipid droplet formation, but its function has remained mysterious. Becuwe et al. show that FIT2 is an acyl coenzyme A diphosphatase, and this activity is crucial for ER homeostasis and cellular lipid storage.
An antibody toolbox to track complex I assembly defines AIF’s mitochondrial function
During mitochondrial complex I (CI) assembly, independently formed assembly intermediates (AIs) merge with each other to form the mature complex. Murari et al. generate a toolbox of 21 antibodies to various mitochondrial proteins and use classical Drosophila genetics and immunoblotting of AIs to define AIF’s role in CI biogenesis.
Mitotic phosphorylation of Pex14p regulates peroxisomal import machinery
The peroxisomal membrane protein Pex14p is phosphorylated in vivo, whereas no function has been assigned to Pex14p phosphorylation in yeast and mammalian cells. Mitotic phosphorylation of Pex14p and consequent suppression of catalase import are a mechanism of protecting DNA upon nuclear envelope breakdown at mitosis.
Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking
GuA1-containing AMPA receptors play a key role in synaptic plasticity and cognition. Casas et al. demonstrate that the sensing of nutrients by CPT1C regulates the phosphatase activity of SAC1, and consequently PI(4)P levels, at the contact sites between the endoplasmic reticulum and the trans-Golgi network to control the trafficking of GluA1 receptors to the cell surface of neurons.
Microtubules and motor proteins support zebrafish neuronal migration by directing cargo
Theisen et al. present mechanistic insights into how microtubules and motors support neuronal migration in zebrafish. The authors demonstrate that microtubules regulate the spatial distribution of crucial migratory factors and propose that this transport capacity of microtubules contributes to neuronal motility.
Collective invasion induced by an autocrine purinergic loop through connexin-43 hemichannels
Khalil et al. show that breast cancer cells release purines into the extracellular space via connexin-43 hemichannels. Extracellular purines activate adenosine receptors and the AKT pathway to induce and maintain leader cell function and collective cancer cell invasion.
Adherens junction regulates cryptic lamellipodia formation for epithelial cell migration
During the collective migration of epithelial cells, interior cells produce “cryptic” lamellipodia to advance. Ozawa et al. show that formation of cryptic lamellipodia is regulated by WAVE and Arp2/3 complexes that accumulate at the adherens junctions. Without this system, cells lose control of their migration.
The RNA binding protein FMR1 controls selective exosomal miRNA cargo loading during inflammation
Wozniak et al. define a novel connection between cleavage of the Rab7 adaptor protein, RILP, and exosome secretion. They demonstrate that inflammasome-mediated RILP cleavage influences sequence-specific miRNA loading into exosomes via interactions with unique cargo vesicles and association with RNA binding proteins.
Tools
Genetically encoded live-cell sensor for tyrosinated microtubules
Intracellular nanobodies as fluorogenic sensors have been developed for many cellular components. Here, we report tyrosination sensor, the first genetically encoded sensor against tyrosinated microtubules. The sensor described here has potential applications to study microtubules and their PTMs in living cells.
Object detection networks and augmented reality for cellular detection in fluorescence microscopy
Waithe et al. use high-performance, low-cost automated microscopy using object detection algorithms to identify and image cells in real time.