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Cao et al. describe the development and application of an engineered protein system (MARS) derived from PLEKHA5 that allows mitosis-specific recruitment of proteins to the plasma membrane to study protein function in cell division.

Park et al. show that cells with impaired autophagy shuttle cytoplasmic proteins to the nucleus for degradation by nuclear proteasomes, revealing synergistic vulnerabilities in diseases where autophagy and nucleocytoplasmic transport are compromised.

Using single-cell RNA sequencing analysis of bone-colonizing tumour cells and in vivo screening, lymphotoxin-β (LTβ) was identified as a key factor promoting bone colonization and outgrowth of breast cancer metastases. Blocking LTβ signalling significantly suppressed bone metastasis, highlighting its potential as a therapeutic target for breast cancer with bone metastatic disease.

Ramskold, Hendriks, Larsson et al. use deep single-cell profiling of newly transcribed RNA to uncover the kinetics and dynamics of transcriptional bursting at allelic resolution in primary mouse cells.

Gasdermins are a family of proteins that form membrane pores and elicit pyroptosis. This Review discusses recent work highlighting their regulation and emerging biological roles, including in non-lethal pore formation and host defence.

In cells migrating through complex three-dimensional microenvironments, microtubules are adaptively reinforced at areas of high compressive stress. This reinforcement controls the release of microtubule-bound contractility effectors to locally modify force generation in space and time, enabling motility and cell survival in mechanically strenuous settings.

Autophagy decreases with age, and this is in part attributed to increasing levels of the autophagy-suppressing protein Rubicon. Cell biologists now find another ageing-associated function for Rubicon — the release of exosomes containing microRNAs that control senescence and longevity.

Yanagawa et al. show that the autophagy-related protein Rubicon recruits WIPI2d to endosomes to promote exosome biogenesis. Rubicon promotes both an increase in exosome release during ageing and the pro-senescent effects of these exosomes.

Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.

Hamazaki, Yang et al. report that an early pulse of retinoic acid robustly induces human gastruloids with a neural tube, segmented somites and more advanced cell types than conventional gastruloids.

Ju et al. show that during three-dimensional cell migration, compression recruits cytoplasmic linker-associated proteins to microtubules; these stabilized microtubules then coordinate nuclear positioning and contractility in confined migration.

Wang, Zhang, Zheng et al. demonstrate that tumour cell-derived lymphotoxin-β activates NF-κB2 signalling and CCL2/5 secretion in osteoblasts to promote bone metastasis in breast cancer, which may potentially be targeted with a decoy receptor in vivo.

Ferroptosis is mediated by toxic accumulation of lipid peroxides. A new study reports that the transcription factor ZEB1 drives ferroptosis sensitivity by regulating the synthesis of highly oxidizable poly-unsaturated fatty acids. This creates a selective vulnerability that can be exploited to eliminate aggressive mesenchymal cancer cells.

Stankunas and Köhler define how the nucleoplasmic portion of the nuclear pore complex (NPC), the basket, docks onto the NPC core by integrating AlphaFold-based interaction screens, electron microscopy, and membrane-templated reconstitutions.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

Kim et al. show that nuclear pore complex (NPC) formation is strongly upregulated during a specific neurodevelopmental window. In neurons, torsinA is required for the maturation and normal localization of nascent NPCs, but not their density.

Helsen et al. use experimental evolution and chromosome engineering to probe the link between karyotype changes and the cell division machinery. They conclude that spindle organization dictates the available trajectories for karyotype evolution.

Majewska et al. show that p16-expressing senescent cells enhance the stability of the immune checkpoint PD-L1 by downregulating its proteasome-mediated ubiquitin-dependent degradation, leading to their accumulation in ageing and chronic inflammation.

Liu, Neve et al. use large-scale loss-of-function RNA-interference screens to identify circular RNAs that are direct regulators of important signalling pathways and also common essential and tissue-specific circRNAs.

Gasdermins (GSDMs) are mediators of cell death that trigger membrane lysis. A study shows that full-length GSDME induces pyroptosis after ultraviolet irradiation, involving GSDME PARylation that releases autoinhibition and lipid reactive oxygen species that promote pore formation. This study adds insights on how GSDMs can be activated non-canonically.