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Spotlights

Liu and Ge highlight work from He et al. that elucidates a phosphorylation cascade that regulates axoneme polyglutamylation and primary cilia function via modulation of ciliary import of tubulin glutamylases.

H.E. Bülow previews a study from Dhanya Cheerambathur and colleagues, which reveals that a kinetochore protein surprisingly regulates dendrite branching by modulating F-actin dynamics.

Cajal bodies are essential sites for the biogenesis of small nuclear and nucleolar ribonucleoproteins. In this issue, Courvan and Parker discuss new work from Neugebauer and colleagues that carefully profiles Cajal Body components and finds an unexpected role for 60S ribosomal proteins.

Reviews

Uytterhoeven et al. review how Tau and α-Synuclein disrupt presynaptic function via converging pathways in Alzheimer’s and Parkinson’s disease and highlight potential therapeutic strategies aimed at preserving synapses.

Reports

Microtubules are vital for diverse cellular processes. Su et al. used CRISPR/Cas9 functional genetic screens to identify factors that affect cell sensitivity to antimicrotubule drugs. This work revealed new roles for established microtubule-associated proteins and identified new players in microtubule function.

Sorensen Turpin et al. investigate the regulation of separase, a key protease required for anaphase onset. They demonstrate that separase localization is precisely regulated to control chromosome segregation and exocytosis during anaphase. The spatiotemporal regulation of separase is an important new aspect of its control.

In Special Collection: Mechanobiology 2025

Orii and Tanimoto study the structural mechanics of microtubule and actin cytoskeletons using high-force intracellular magnetic tweezers. The measurements directly reveal the integrated nature of the two cytoskeletons throughout the cytoplasm, which defines their physical behavior as a simple cell-scale continuum.

Ramakrishnan et al. describe a larval zebrafish model of early melanoma invasion that is amenable to real time imaging of the dynamic interactions between macrophages and invading tumor cells. The work highlights a role for Rac2 signaling in macrophages during early melanoma invasion.

Articles

Corepressors in the TPL/TBL1-type family prime genes for rapid activation by facilitating assembly of the transcription preinitation complex, including TFIID and SPT proteins.

This study identifies new Cajal body components and tests their roles in the formation of these nuclear membraneless organelles. Imbalances in the levels of nuclear dimethylarginine are caused by the depletion of ribosomal proteins and are associated with changes in CB number and shape.

MinD oscillations adapt to cell growth by modulating concentration gradients through dynamic protein interactions and diffusion, ensuring accurate division site placement. This study provides a quantitative understanding of Min oscillations, emphasizing the system’s plasticity and adaptability in the cellular environment.

Polyglutamylation, a major posttranslational modification of tubulin on the axoneme, is crucial for the signaling functions and stability of primary cilia. In this study, the authors identified a novel CDK7-CDK6-FIP5 phosphorylation cascade that regulates axoneme polyglutamylation and primary cilia function by controlling the ciliary import of tubulin glutamylases.

In Special Collection: Cancer Cell Biology 2025

We have discovered a druggable PARP14/TARG1-regulated pathway that mediates site-specific mono(ADP-ribosyl)ation of RACK1, a ribosomal protein. This pathway controls stress granule assembly and disassembly, as well as the translation of a subset of mRNAs, to modulate the growth of ovarian cancer cells in culture and in vivo.

In Special Collection: Immune Cell Biology 2025

Langerhans cells (LCs) are resident immune sentinels of the skin. Autophagy supports metabolism in particular environments. Abrogation of autophagy in LCs leads to lipid accumulation and ferroptosis-mediated depletion, demonstrating that this pathway is necessary for LC maintenance in the epidermis.

ATG9A contributes to the final stage in autophagosome biogenesis by directing autophagosome closure. It does so by recruiting ESCRT protein CHMP2A via IQGAP1. Thus, ATG9A contributes to all steps in autophagosome biogenesis, from initiation through expansion to the final membrane closure.

LRRK2 is a kinase whose activity is linked to Parkinson’s disease. This study identifies a pathway that links LRRK2 activation to lysosome perturbations. This pathway involves the process known as CASM and culminates in an interaction between LRRK2 and GABARAP at the surface of lysosomes.

This study reveals inherent perforations in neuronal endolysosomal membranes, facilitating cytosolic α-synuclein’s access to internalized fibrils and triggering toxic α-synuclein aggregation. This pathway highlights a specific mechanism in synucleinopathies.

Alves Domingos et al. uncover a non-cell-division-related function for the kinetochore protein KNL-1 in dendrite arborization. They show that KNL-1 regulates the actin cytoskeleton in the highly arborized Caenorhabditis elegans PVD neuron and harbors an intrinsic ability to promote F-actin assembly at the plasma membrane.

Tools

The 4× and 12× 3D-ExM methods were optimized for super-resolution expansion microscopy, offering a one-step expansion process without the need for specialized equipment or conditions. We rigorously validated their robustness, reproducibility, isotropy, and preservation across diverse subcellular structures and microorganisms, making these user-friendly techniques widely accessible for cell biology research.

Gameiro, Juárez-Núñez et al. establish genome-wide libraries of conditional auxin-inducible degron alleles in budding yeast and demonstrate how these resources can be applied to uncover gene functions, thus adding to the toolkit for functional genomics in this organism.

Valenti et al. created a proteome-wide yeast degron library for rapid in vivo protein depletion. This tool enables dynamic protein function studies with minimal cellular rewiring, advancing beyond prior collections. It highlights applications for inducible protein depletion, deepening insights into cellular physiology.

Wuergezhen et al. developed a Col4a2 fluorescently tagged mouse model to reveal a spatial gradient in basement membrane (BM) turnover and expansion during hair follicle development. Inhibition of matrix metalloproteinases alters BM turnover, expansion and epithelial progenitor behaviour, ultimately impacting hair follicle morphology.

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