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Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Cui et al. find that arginine depletion and inflammation reduces nuclear localization of arginyl-tRNA synthetase, which influences alternative splicing via condensate-like serine/arginine repetitive matrix protein 2, and regulates cellular metabolism and response to inflammation.

This study reveals how a cancer-associated mutation in CHD1 leads to the loss of its C-terminal intrinsically disordered region, disrupting condensate formation. This impairment causes improper genome distribution and gene expression, driving cancer development.

Cryo-electron microscopy, in vitro reconstitution and molecular dynamics simulations provide insight into the architecture of a plasma membrane microdomain in yeast, the organization and dynamics of the membrane lipids within this microdomain and how it responds to mechanical stress.

The understudied lipid kinase PIP4K2C binds SARS-CoV-2 nonstructural protein 6 and regulates virus-induced autophagic flux impairment, suppressing viral protein degradation. PIP4K2C inhibition is a candidate strategy to combat emerging viruses.

Vietri et al. show that the micronucleus fails to restrain ESCRT-III spreading due to its small size, resulting in aberrant accumulation of ESCRT-III to drive micronuclear collapse and DNA fragmentation.

Here the authors show that human pancreatic islets adapt during pregnancy with increased α-cell area and GLP-1 abundance, while key differences from islet adaptations in mouse pregnancy include unchanged β-cell PRLR abundance and absent β-cell 5-HT_2B receptor expression.

Kwak et al. report that adherens junctions organize membrane microdomains, leading to lipid-dependent γ-secretase recruitment and size-dependent protein segregation, excluding full-length Notch receptor.

Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited incurable legal blindness. Here the authors demonstrate that conjugated polymer nanoparticles reinstate visual functions in aged rats with fully degenerated and rewired retinas.

Viral pathogens frequently target host cell antigen-processing pathways, including MHC-I–TAP peptide transporters, to evade host immunity. Blander and colleagues describe how MHC-I molecules can still cross-present antigen by re-routing ERGIC-resident MHC molecules to phagosomal vesicles, where phagolysosomal proteases act to shape the peptide repertoire for MHC-I presentation.

The endosomal retrieval subdomain organizes recycling of endocytosed proteins. Here, using proximity proteomics, the authors reveal that this recycling subdomain regulates switching of specific RAB GTPases, a feature likely important in neuroprotection.

Real time cellular fluorescence imaging requires a probe that displays high degrees of localisation, low toxicity and good photostability. Here, the authors report a near infrared fluorophore that displays pH-sensitive fluorescence based on phenol/phenolate interconversion, showing real time imaging of cellular processes.

Kim and coworkers describe a technique, EPSILON, to map AMPA receptor exocytosis, a proxy for synaptic plasticity, in mice. The authors demonstrated a correlation between AMPA receptor exocytosis and cFos expression during a fear conditioning experiment.

Live-cell single-molecule imaging of pioneer transcription factors revealed a ‘confined target search’ mechanism where they alternate between fast free diffusion in the nucleus and slower confined diffusion within compacted chromatin domains, leading to efficient pioneering on closed targets.

Kaposi’s sarcoma-associated herpesvirus changes mitochondrial architecture via vBcl-2 interaction with a host NDP kinase, which triggers mitochondrial fission and inhibition of MAVS allowing for virus production.

Dual functions of MX2 in innate immunity against HIV-1 and nuclear import of cellular proteins are regulated by phosphorylation.

Bcl-2 interacting killer (Bik) decreases airway epithelial hyperplasia via apoptosis mediated by calcium release from the endoplasmic reticulum (ER), but the mechanism is unclear. Here the authors show that Bik promotes Bak enrichment at the ER to tether mitochondria for efficient calcium transfer.

Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.

Accurate repair of DNA damage is crucial for genome stability and preventing disease. Here, the authors adapt single-cell omics technologies to map the location of repair proteins across the human genome, showing formation of multi-way chromatin hubs in response to damage.

GABA_B receptors mediate the effects of the main inhibitory neurotransmitter in the brain. Here, authors identify the cytoskeletal protein filamin A as a key player that controls the exact location and function of GABA_B receptors at the cell surface.

Spatial and single-nucleus analyses in human postmortem Alzheimer’s disease (AD) brain tissues at early and late stages from individuals with and without Down syndrome, as well as in AD mouse models, show sex and species-specific phenotypic changes.

Arbovirus has co-evolved with its insect vector, enabling efficient and persistent transmission by vectors. Here, the authors reveal an immune homeostatic mechanism shaped by apoptosis and autophagy that facilitates arbovirus preservation within its whitefly vector.

KRAS is a small GTPase that regulates cell proliferation. Here, the authors show that a subset of cell surface glycosphingolipids regulate KRAS plasma membrane localization by modulating inner leaflet lipid composition, uncovering a requirement for KRAS oncogenesis that may have therapeutic potential.

A pH-responsive, soft polymeric nanoparticle targets the neurokinin 1 receptor in acidified endosomes to inhibit signalling events leading to chronic pain.

Nucleotide sugars are transported from the cytoplasm to the Golgi lumen where they are incorporated into cell wall polysaccharides and used for glycosylation of proteins and lipids. Here the authors identify GFT1, an ArabidopsisGolgi-localized GDP-fucose transporter that is required for plant growth and development

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

Park et al. show that in the process of metastasis, dying tumor cells enhance the outgrowth of their surviving counterparts via nuclear expulsion, resulting in an extracellular DNA–protein complex that activates RAGE receptors on tumor cells.

While neutrophils are the first line of defence against infections and inflammation, their unrestricted recruitment and constant activation might result in prolonged inflammation and sharpening of specific pathological conditions. Here the authors develop a strategy to specifically target activated, pro-inflammatory neutrophils and neutrophil–platelet complexes to deliver therapeutics in the context of a murine model of venous thrombosis.

Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

Integrative anatomical, molecular, behavioral, and modeling evidence suggests that higher dopamine D1 receptor expression in prefrontal cortical parvalbumin neurons in marmosets likely contributes to their higher distractibility relative to macaques.

Obesity-induced mitochondria stress and dysfunction results from disorganized mitochondria-associated ER membranes and excess calcium flux.

VARP is bound to endosomes and functions as a protein:protein interaction platform. Here, the authors present the NMR structure of the complex between the retromer subunit VPS29 and a VARP Zn-fingernail microdomain that is structurally distinct from Zn-fingers and further show that mutations, which abolish VPS29:VARP binding, inhibit trafficking from endosomes to the cell surface.

Moliner et al. show that psychedelics directly bind to the BDNF receptor TrkB with high affinity and promote BDNF-mediated plasticity and antidepressant-like effects, whereas their hallucinogenic-like effects are independent of TrkB binding.

At high cell density or when plated on soft matrix, YAP/TAZ are redistributed from the nucleus to the cytosol, becoming transcriptionally inactive. Here the authors show that at high cell density, autophagosome formation is impaired due to reduced YAP/TAZ-dependent transcription of actomyosin genes

3D hydrogels have provided information on the physical requirements of stem cell fate, but the contribution of interactions with the pericellular environment are under-explored. Here the authors show that pericellular matrix secreted by human bone marrow stromal cells (hMSC) embedded in a HA-based hydrogel contribute to hMSC fate.

Mitochondrial dysfunction results in the accumulation of mitochondrial proteins in the cytosol. Here, the authors show that the immunoproteasome subunit PSMB9 promotes protein degradation to maintain cellular protein homeostasis.

A modular anti-albumin nanobody conjugated to a STING agonist enhances antitumour immunity by improving pharmacokinetics, tumour accumulation and immune responses, inhibiting murine tumour growth and enhancing cancer immunotherapies.

Modifying the polyethylene glycol lipid ratio and phospholipids in the lipid nanoparticle component of nucleoside-modified mRNA–lipid nanoparticle vaccines is shown to have an impact on the elicited cellular and humoral immune responses.

Wu, Harrison and colleagues visualize lactate production at subcellular resolution in migrating endothelial cells and identify hotspots of glycolytic activity, mediated by RhoA and the glucose transporter SLC2A3, that couple cellular energy metabolism with cytoskeleton remodelling and cell motility.

There is growing evidence that autophagy might serve specialized functions in neurons besides its role in protein homeostasis. In this study, authors demonstrate that axonal retrograde transport of BDNF/TrkB in neuronal amphisomes is involved in plasticity-relevant local signaling at presynaptic boutons and that SIPA1L2, a member of the SIPA1L family of neuronal RapGAPs, associates via LC3b to TrkB-containing amphisomes to regulate its motility and signaling at the axon terminals

TMEM16K is a member of the TMEM16 family of integral membrane proteins that are either lipid scramblases or chloride channels. Here the authors combine cell biology, electrophysiology measurements, X-ray crystallography, cryo-EM and MD simulations to structurally characterize TMEM16K and show that it is an ER-resident lipid scramblase.

Urra et al. discover that IRE1α, an ER stress mediator, interacts with filamin A and controls actin dynamics and cell migration in mouse, Drosophila and zebrafish models in a manner independent of its canonical function.

Hepatitis E virus exists in two forms in patients: naked and quasi-enveloped. Using a new imaging method, the authors found that these forms enter cells through different pathways, directed by interaction of the capsid protein with integrin beta 1.

Here, the authors present Protein Interface-score (PI-score), a machine learning-based metric that has been trained on protein–protein interfaces’ features from high-resolution crystal structures. They use the PI-score to evaluate the protein–protein interfaces in more than 1000 PDB-deposited cryo-EM structures and show that it can be used as a complementary assessment tool for cryo-EM model validation.

Streptococcus mutans (S. mutans) has been implicated as a major pathogen in childhood caries. Here, the authors show that Selenomonas sputigena, a flagellated anaerobe, interacts with S. mutans in the supragingival biofilm, builds a honeycomb-like multicellular-superstructure that encapsulates it, and promotes the development of childhood dental caries.