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Article
Identification of coilin interactors reveals coordinated control of Cajal body number and structure
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.
The kinetochore protein KNL-1 regulates the actin cytoskeleton to control dendrite branching
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.
RACK1 MARylation regulates translation and stress granules in ovarian cancer cells
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.
Neuronal constitutive endolysosomal perforations enable α-synuclein aggregation by internalized PFFs
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.
Epidermal maintenance of Langerhans cells relies on autophagy-regulated lipid metabolism
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 facilitates the closure of mammalian autophagosomes
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.
A function of TPL/TBL1-type corepressors is to nucleate the assembly of the preinitiation complex
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.
Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation
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.
Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli
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.
Report
Securin regulates the spatiotemporal dynamics of separase
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.
Functional genetics reveals modulators of antimicrotubule drug sensitivity
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.
Real-time imaging reveals a role for macrophage protrusive motility in melanoma invasion
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.
Structural response of microtubule and actin cytoskeletons to direct intracellular load
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.
Tools
An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis
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.
One step 4× and 12× 3D-ExM enables robust super-resolution microscopy of nanoscale cellular structures
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.
Genome-wide conditional degron libraries for functional genomics
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.
A proteome-wide yeast degron collection for the dynamic study of protein function
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.
Review
Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health
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.
Spotlight
Regulation of Cajal bodies: Unexpected connection to 60S ribosomes
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.
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