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Issues

Spotlights

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.

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.

Matikainen et al. preview work from Wozniak et al. that reveals that inflammasomes mediate sequence-specific miRNA loading into exosomes.

Perspectives

In Special Collection:
2020 Nobel Prize Collection

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

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

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.

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.

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.

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.

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

In Special Collection:
Special Focus

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.

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.

In Special Collection:
Editors’ picks 2021

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 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.

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.

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.

In Special Collection:
Cellular Neurobiology 2020

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.

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.

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.

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.

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

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.

Waithe et al. use high-performance, low-cost automated microscopy using object detection algorithms to identify and image cells in real time.

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