Issues

Vaquero-Pelaz D et al. show that the kinase Sak1 activates separase, promoting its nuclear accumulation and mitotic function. A hypermorphic SAK1-E50K allele boosts separase activity, while human LKB1 associates with separase, revealing a conserved kinase-protease regulatory axis.

Wu et al. provide in vivo evidence for the long-proposed role of the Ras effector Ral, a small GTPase, in regulating the metazoan exocyst complex. Using endogenous proteins and structure-guided genetics in C. elegans, they show that conserved Ral–exocyst interactions are required for vesicle trafficking, secretion, and tissue morphogenesis.

Proper neuromorphogenesis is pivotal for neuronal network formation and brain function. Jain, Izadi-Seitz and Ji et al. identify mechanisms and cellular functions of the N-Ank protein Ankrd24 in shaping nerve cells by coordinating remodeling of membrane topologies and of cytoskeletal structures and thereby shed light on proper neuronal arbor development.

All cells experience mechanical forces, yet how they increase energy production to meet the demands of force response remains incompletely understood. This study identifies a key missing link, providing evidence that the muscle isoform of the rate-limiting glycolytic enzyme phosphofructokinase is recruited to actin, thereby serving this important role.

Using computational protein–protein interaction screens, Vignogna and Fromme identify Avl9 as a GTPase-activating protein for Arf-family GTPases. They demonstrate that Avl9 and related DENN-domain proteins constitute a previously unrecognized group of GAPs, revealing unexpected functional diversity within this protein family.

Using iPSC-derived human neurons gene-edited to express pathogenic KIF1A variants, Aiken et al. demonstrate that distinct alterations in KIF1A motor function disrupt synaptic development through divergent cellular mechanisms, providing new insight into the pathogenesis of KIF1A-associated neurological disorder.

Sydir et al. identify an ESCRT-independent pathway for nuclear envelope assembly in S. japonicus that involves the conserved proteins, Vid27 and Alx1. This work sheds light on alternative nuclear envelope assembly processes that may explain why the Cmp7/ESCRT-III pathway is not essential in a number of organisms and cell types.

Gourkanti et al. show that the rhomboid protease Rhbdl2 restrains macrophage recruitment and wound repair in zebrafish. Loss of Rhbdl2 enhances macrophage accumulation and migration speed at wounds via elevated Rac2, accelerating tissue regeneration, positioning Rhbdl2 as a potential brake on macrophage-driven repair with relevance to inflammatory and fibrotic disease.

How cells adapt their membranes to prolonged stress is poorly understood. Williams et al. show that chronic hyperosmotic stress triggers lipid droplet accumulation and a shift toward phosphatidylcholine in budding yeast. Triacylglycerol synthesis supports adaptive changes in membrane properties, while elevated phosphatidylcholine promotes cell fitness.

Sheu-Gruttadauria et al. show that the material properties of the nucleolus are shaped by the assembly state of ribosomal precursors, which tune nucleolar dynamics and morphology through their interactions with the nucleolar scaffolding protein NPM1.

Abir Elfarkouchi, Arthur Vitard et al. reveal the first structural model for CM1 domain autoinhibition, which prevents ectopic binding and activation of microtubule-nucleating γ-tubulin ring complexes. The model shows that intramolecular hairpin folding and species-specific domain associations sequester critical binding residues. In addition, they uncover key evolutionary divergences in how the CM1 binds γ-tubulin ring complexes.

Metti et al. show that ECM turnover in skeletal muscle depends not only on proteases but on receptor-mediated uptake. ANTXR2, a membrane receptor of fibro-adipogenic progenitors, clears collagen VI from connective tissue, and its loss stiffens muscle and impairs locomotion, shedding light on muscle pathology in hyaline fibromatosis syndrome.

Lemonnier, Dumont, and colleagues show that reproductive aging is associated with weakened centromere function and altered spindle microtubule organization in mammalian oocytes. Their findings support a role for reduced CENP-A–dependent centromere function in chromosome segregation errors and highlight multiple vulnerabilities that may compromise egg quality with advancing maternal age.

Huizar et al. show that E-cadherin promotes breast cancer cell survival and metastasis by suppressing mitochondrial ROS. The cytoplasmic domain of E-cadherin is essential, while extracellular domains, and adhesion and catenin interactions are not. Thus, E-cadherin’s regulation of mitochondrial ROS and cell survival during metastasis is independent of cell–cell adhesion.

Clegg et al. show that LRRK2 integrates distinct lysosomal stress signals through stimulus-specific combinations of interactions with Rab GTPases and GABARAP. PIKfyve inhibition activates LRRK2 through ClC-7–dependent accumulation of a subset of Rabs on lysosomes without requiring GABARAP, whereas CASM-inducing stresses require both Rab and GABARAP interactions.

Du et al. identify the atypical VAP-family protein MOSPD3 as an ER receptor for the lipid-transfer protein ATG2A. MOSPD3 uses its MSP domain to capture an FFNT motif in the ATG2A N terminus, anchoring the ATG2A lipid-transfer bridge at ER–phagophore contacts to support autophagy.

Zhao et al. develop constitutive and inducible Golgi reporter mice that enable in vivo visualization of Golgi architecture and Golgiphagy at single-cell resolution. Their study reveals tissue-specific Golgiphagy heterogeneity and stress-induced Golgi remodeling, providing a powerful platform to investigate Golgi homeostasis, disease mechanisms, and therapeutic opportunities.

Hickson revives a material-processing view of cytokinesis, asking how a shrinking membrane–cortex interface sustains closure despite continued material inflow.

Niwa highlights recent work by Aiken et al. describing how different pathogenic KIF1A variants affect synapse development.

Pfeffer discusses work from Clegg et al. showing that PIKfyve inhibition swells lysosomes, traps Rab GTPases, and activates LRRK2 without the GABARAP–CASM pathway.