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It is shown that a mitochondrial protein, mitofusin 2, is enriched at the mitochondrial–endoplasmic reticulum interface and mediates tethering of both organelles. Ablation of mitofusin 2 results in disruption of endoplasmic reticulum morphology and loss of calcium transfer between the two organelles. Thus, mitofusin-2 mediates tethering mitochondria to the endoplasmic reticulum.

A genome-wide RNA interference analysis identifies the septin family of cytoskeletal filaments as important regulators of store-operated Ca²⁺ entry into the cell; septins are shown to organize plasma membrane microdomains important in STIM1 and ORAI1 signalling, and may also be relevant in membrane microdomains underlying other signalling processes.

Eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that exist at the kilo-megabase scale. Here Cattoni et al. combine super-resolution microscopy with DNA-labeling methods to quantify absolute frequencies of interactions within TADs.

The use of an endoplasmic reticulum–localized HaloTag system results in protein destabilization and activation of a transient unfolding protein response (UPR) without causing cell death, allowing the examination of later stage UPR events.

Zanin, Viaris de Lesegno et al. identify what controls the endosomal activation of the IFNAR receptor by IFN-α and establish a central role for endosomal sorting via STAM and Hrs in the differential regulation of JAK–STAT signalling by IFN-α and IFN-β.

The multipass membrane transporter MFSD6 localizes to the plasma membrane and acts as a host entry factor for enterovirus D68 (EV-D68) by binding directly to EV-D68 particles through its extracellular, third loop, offering a potential target to combat infections by this emerging pathogen.

In most eukaryotes, the centromere is defined by epigenetic marks such as the histone H3 variant CENH3/CENP-A/CID. Ectopic induction of kinetochores in Drosophila S2 cells by CID overexpression leads to kinetochore assembly specifically in silent intergenic regions bordering heterochomratin, demonstrating a role for these domains in centromere identity.

Odinstova, Mohammed, Trieber et al. use structure-based mutagenesis to identify key residues in human periplakin and desmoplakin linker modules required for co-localization with vimentin intermediate filaments. They show that vimentin D176 and E187 are required for direct binding with the periplakin linker.

Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.

The active zone is a brain signaling hub critical for synaptic information transfer and the encoding of behaviors. The authors identify Blobby as an assembly factor required for proper active zone nanoscale protein architecture and memory formation.

Ferroptosis is a lipid-peroxide-driven cell death with promising therapeutic applications. Although peroxidation of various subcellular membranes can initiate ferroptosis, the authors found that the endoplasmic reticulum is an essential site.

RNA polymerase II with a hypophosphorylated C-terminal domain preferentially incorporates into mediator condensates, and with a hyperphosphorylated C-terminal domain into splicing-factor condensates, revealing phosphorylation as a regulatory mechanism in condensate preference.

A series of fluorescent probes is designed that act as dual agonists on both GLP1 and GIP receptors, and are used to image receptor binding activities in tissues and animals.

Biochemical and microscopy studies show that IF1 is the in vivo regulator of active/inactive state transitions of the ATP synthase and is required for ATP synthase oligomerization determining the heterogeneity of the membrane potential of cristae.

The plant commensal Bacillus velezensis SQR9 uses its type VII secretion system to deliver effector protein YukE to plant roots, which causes iron leakage and promotes its colonization on roots.

SARS-CoV-2 has been shown to induce IL-1β-mediated neuroinflammation in humans and rodent models. Klein and colleagues show that low-dose COVID-19 vaccination prevents breakthrough infection-mediated hippocampal dysfunction and cognitive memory decline in mouse models.

Anti-NMDA receptor encephalitis is the most common autoimmune encephalitis. Michalski et al. reveal epitope diversity, conformational changes and functional impacts of the autoantibodies using cryo-EM and electrophysiology.

Sissoko et al. show that CENP-T local concentration regulates its ability to recruit the outer kinetochore, which may restrict complete kinetochore formation to regions with higher-order inner kinetochore assemblies.

Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.

A mass spectrometry–based approach is used to investigate the mechanisms by which different NUP98 fusion proteins cause leukemia, revealing that the fusion proteins share common interactors and alter the composition of nuclear condensates.

Extrachromosomal DNA (ecDNA) congregates in clusters called ecDNA hubs that promote intermolecular interactions between gene-regulatory regions and thereby amplify the expression of oncogenes such as MYC in cancer cell lines.

The way in which metastatic tumour cells control endocytic vesicular trafficking networks to establish a front-rear polarity axis that facilitates motility remains unclear. Here, the authors show that the EMT activator ZEB1 influences vesicular trafficking dynamics to execute cell polarity change.

Cells transmit mechanical force to the nucleus via the cytoskeleton. Here, the authors reveal a role for the actin regulator Mena in force transmission at the nuclear envelope, where it regulates nuclear architecture, chromatin organization and gene expression.

STING is an intracellular sensor of pathogen- or host-derived DNA. In this study, the authors identify an ESCRT complex that regulates STING degradation, thus acting as a homeostatic regulator of STING signalling and type-I interferon responses.

The innate antiviral immune response is an important defense against infection. Here, the authors show that leukocyte cell-derived chemotaxin 2 (LECT2) promotes RIG-I-mediated innate immune responses by preventing its degradation, and inhibits lymphocytic choriomeningitis virus replication in the liver.

Clathrin light chains (CLCa and CLCb) are major constituents of clathrin-coated vesicles. Here authors find and structurally characterize the selective interaction between CLCa and the actin motor protein myosin VI which act together to generate the force that leads to invagination and fission at the apical surface.

Three-dimensional imaging reveals the existence of GPCR domains at the plasma membrane of living cells. The molecular mechanism underlying this spatial organization is energetic coupling of receptors to the curvature of the plasma membrane.

Specificity in signaling activated by receptor tyrosine kinases is typically attributed to characteristics of their intracellular domains. Here, the authors demonstrate that an extracellular receptor sequence motif controls intracellular signaling as a result of extracellular glycan interactions.

Pulsatile GABA secretion from human beta cells via the volume regulatory anion channel (VRAC) and subsequent uptake by the GABA-permissive taurine transporter (TauT) is shown to regulate total insulin secretion and pulsatility.

The effect of IFITM3 on viral pathogenesis is poorly understood. Here, the authors show that IFITM3 restricts cytomegalovirus pathogenesis by reducing Nogo-B-mediated inflammation in response to viral stimuli.

Caveolae are mechanosensors and mutations of their coat proteins are implicated in muscle disorders, but molecular mechanisms are unclear. Here, the authors show that caveolae can regulate IL6/STAT3 signaling in muscle cells under stress, and that dystrophy related Cav3 mutant myotubes have reduced caveolae and upregulated IL6 signaling.

The molecular circuitry that drives dendrite formation during osteocytogenesis remains poorly understood. Here the authors show that deletion of Sp7, a gene linked to rare and common skeletal disease, in mature osteoblasts and osteocytes causes severe defects in osteocyte dendrites.

This study shows that cardiac injury induces cardiac fibroblasts to undergo mesenchymal–endothelial transition and acquire an endothelial-cell like fate, a process mediated, in part, by a p53-dependent mechanism — use of a small molecule activator of p53 increases mesenchymal–endothelial transition, leading to reduced scarring and better preservation of heart function.

Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.

IRE1α plays a key role in the unfolded protein response (UPR) by promoting the unconventional splicing of the XBP1 and the selective cleavage of RNAs. Here the authors report that IRE1α is activated upon the DNA damage response and selectively controls the stability of mRNAs to maintain genome integrity.

The L protein of segmented, negative strand RNA viruses contains the RNA-dependent RNA polymerase essential for virus amplification. Here, the authors report cryoEM structures of the Lassa virus L protein in active, RNA-bound states, and provide mechanistic insights.

It was known that prolonged TRMPL1 activation induces TFEB translocation and upregulates autophagic gene regulation. Here, the authors show that acute TRMPL1 activation also induces autophagy through VPS34 and by lysosomal calcium release independent of TFEB.

The authors define a specific cortical subregion of the somatosensory cortex as a critical region of dysfunction that is causal to the emergence of abnormal social and repetitive behaviours in mice exposed to maternal inflammation.

Starvation triggers autophagy by inhibiting mTOR signalling. Here, Moreau et al.identify an alternative, transcriptional activation pathway: starvation-induced JNK signalling upregulates Annexin A2 transcription, which in turn enhances actin-dependent transport of Atg9 vesicles from endosomes to autophagosomes.

Establishment of the outer blood-retina barrier is a hallmark of retinal development but the contribution of choroid endothelial cells (ECs) is not known. Here the authors show in the developing mouse retina that ECs remodel the basement membrane and lead to enhanced barrier function of retinal epithelial cells.

Polycomb group proteins are epigenetic gene silencers that are thought to exist in two biochemically distinct multiprotein complexes, termed PRC-1 and -2. Here, Cao et al.show that EED, a core component of PRC2, interacts with and functions as part of PRC1, thus coordinating the activities of both complexes.