Issues

Kawauchi and Ito discuss recent work from Kim et al. on how pediatric glioma cells migrate on neurons, astrocytes, and the extracellular matrix.

Rachel Kadzik and David Kovar preview work from Chikireddy and colleagues, which examines how fascin delays cofilin-induced actin filament disassembly and regulates network turnover.

Isogenic pools of tumor cells can undertake different invasion strategies, frequently attributed to cell-extrinsic factors such as ECM or the intervention of stromal cells. In this issue, Friedl and Zegers discuss new work by Marcus and colleagues that finds paracrine signaling from collectively invading cells induces dissemination of single cells in the same population.

Bernardes and Chook preview work from Yang et al. that reveals that folded WW domains can serve as nuclear localization signals.

Campanella and Kannan discuss the emerging knowledge of the molecular composition and function of mitochondrial–nuclear contact sites in eukaryotes.

Bhandari and Brandizzi review the trafficking pathways recruited upon plant defense activation and how these pathways are targeted by pathogens to dampen immunity and cell wall fortifications resulting from immune activation.

Xiong and Sheng review recent advances in presynaptic mechanisms of neurodevelopmental disorders by focusing on impaired axonal transport of presynaptic cargos.

Autophagy is a cellular degradation program that counts xenophagy, the engulfment and destruction of cytosolic pathogens, among its many functions. Here, Krause et al. show that cytosolic replicating poxviruses disarm xenophagy during early infection by targeting a subset of autophagy receptors required for pathogen detection.

The ability to repair plasma membrane damage is essential to cell survival. Here, the authors demonstrate that the mobilization of phosphatidylserine to sites of membrane damage aids the assembly of tetraspanin rings and ultimately the cellular membrane repair response through the actions of ORP5 and ORP9.

Zens et al. present a workflow to structurally characterize natively preserved extracellular matrix (ECM) using lift-out cryo-FIBSEM and cryo-ET. Employing cell-derived matrices to mimic authentic ECM, they reveal the intricate network of extracellular fibers in the context of matrix-secreting cells. Their findings expand the structural atlas of the ECM.

Yang et al. report a novel class of nuclear localization signals served by the family of WW domains, termed WW-NLS, to elucidate the nuclear import mechanism of YAP1 and thus propose a new strategy to interfere with YAP1-dependent cancer progression.

The study uncovers the pivotal role of PCIF1-mediated m⁶Am RNA modification in ciliogenesis. PCIF1 negatively regulates ciliation by modulating BICD2 protein levels via m⁶Am catalytic activity, influencing mRNA stability and translation efficiency. These findings elucidate a fundamental mechanism in ciliogenesis regulation.

Ward et al. demonstrate that in addition to its well-established role as a positive regulator of proteasome genes, the transcription factor Nrf1/NFE2L1 can also induce autophagy–lysosomal pathway (ALP) genes and drive autophagic flux in response to proteotoxic stress.

Chikireddy et al. investigate how crosslinker fascin delays cofilin-induced actin filament disassembly. Fascin hampers the initial formation of cofilin clusters, triggering interfilament cooperativity, which favors subsequent cluster formation but does not enhance severing per cluster. This study deciphers the role of crosslinkers in actin turnover.

Li et al. reveal that liquid–liquid phase separation of host fragile X–related (FXR) family proteins drives clustering of replication organelles of SARS-CoV-2 via specific interaction with viral nonstructural protein Nsp3. FXRs further recruit translation machinery to facilitate viral protein translation for efficient viral replication.

LET-767, a member of hydroxysteroid dehydrogenase, interacts with ADP-ribosylation factor 1 (ARF-1) to prevent ARF-1 lipid droplet (LD) translocation for appropriate LD protein targeting. Deficiency of LET-767 triggers ARF-1 and ATGL-1 (adipose triglyceride lipase) LD translocation, leading to displacement of LD proteins and promoted lipolysis.

Ripin et al. demonstrate that the DEAD-box helicase DDX6, a known P-body component, can also limit the formation and composition of stress granules, while also identifying P-body components that modulate the docking between P-bodies and stress granules.

SM proteins catalyze accurate assembly of SNARE prefusion complexes. The SM Sly1 operates at early secretory organelles. Duan et al. show that Sly1 directly contacts incoming vesicle membranes. This both activates Sly1, and tethers vesicle and target membranes at close range to promote SNARE-mediated fusion.

SM proteins are essential SNARE cofactors for membrane fusion. The ER–Golgi SM, Sly1, has several different activities reported to promote fusion. Here, Duan et al. test each function in parallel genetic and biochemical reconstitution experiments. The results show that all of them are important for efficient fusion. A working model for the order of events is presented.

Dou et al. demonstrate that Parkinson’s disease-associated hyperactive LRRK2 decreases the trafficking of synaptic vesicle proteins within neurons by disrupting the regulation of the synaptic vesicle precursor protein RAB3A. Impaired delivery of synaptic proteins to presynaptic sites could contribute to the progression of debilitating non-motor PD symptoms.

Füllbrunn et al. show that the Rab7/Ypt7-specific GTPase activating protein Gyp7 localizes to endosomes, where it is required for Ypt7 regulation. Manipulation of Gyp7 affects both Ypt7 localization and TORC1 signaling, suggesting a link between the endosomal Ypt7 pool and nutrient signaling.

Pediatric gliomas invade the brain by migrating between nerve cells or exploiting extracellular matrix along blood vessels. This research reveals crosstalk between YAP1/TAZ signaling and N-cadherin that regulates leader–follower cell phenotypes and migration efficiency in neural and extracellular matrix environments.

Collectively invading cells and single cells co-exist within a heterogeneous tumor. Collectively invading cells abundantly secrete laminin-332, which bolsters the invasion of single cells via Rac1 activation through integrin α6/β4 binding. This finding suggests a novel commensal interaction between invasive distinct subpopulations.

Maib et al. present a toolbox of recombinant biosensors for the multiplex and super-resolution detection of phosphoinositides, a small family of signaling lipids. Detection of these crucial lipids in fixed cells and tissues will enable researchers to address key outstanding questions in cell biology.