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Spotlights

Han and Miao highlight recent findings from Magliozzi et al. identifying a novel “composite” actin nucleator for the assembly of thick actin cables.

Juan Martin-Serrano highlights work from Dam, Moreno, Brownlow, and colleagues, which reveals how Srs2/PARI act as a missegregated chromatin sensor for NoCut, delaying cytokinetic abscission.

Anthony Morgan highlights a new reporter for endo-lysosomal Ca2+ developed by Calvo et al. and discusses the potential implications of Ca2+ stores in the endo-lysosomal system.

Viewpoint

Mast et al. challenge the PPAR paradigm and show human peroxisomes expand via hominid-specific pathways that link specialization to immunometabolic functions.

Reports

Avilov et al. used quantitative phosphoproteomics in starfish oocytes to identify downstream targets of the conserved Mos–MAPK pathway. This reveals how Mos–MAPK may alter the cell cycle and the organization of the spindle to switch from the mitotic to the reductional and asymmetric meiotic division program.

Tubular ER extends into retraction fibers and migrasomes through microtubule-dependent ER extension and ER-plasma MCSs in migrating cells. MCSs facilitate cholesterol/calcium transfer to migrasomes, supporting their biogenesis and long-range, site-specific signaling transduction. This reveals a novel distal ER-mediated mechanism for localized lipid/ion transmission and secretion.

Deng et al. employ two human cell models to elucidate how tubulin binding, membrane association, and protein stability converge in the biology of STMN2, a protein implicated in amyotrophic lateral sclerosis. This work represents the first direct investigation of the interplay between STMN2’s membrane association and tubulin binding, offering broad implications for neurodegeneration research.

Articles

Dam, Moreno, Brownlow et al. identify Srs2 as a key mediator of abscission inhibition in yeast and show that its human paralog PARI regulates abscission-associated events. Their findings suggest an evolutionarily conserved mechanism linking chromatin bridge detection to cytokinesis timing.

Beyond its canonical ARF GEF role in synaptic LTD, IQSEC2 undergoes Ca2+-dependent phase separation to scaffold and dynamically modulate postsynaptic protein complexes, enabling bidirectional regulation of synaptic strength.

Li et al. reveal that Aurora A–mediated phosphorylation of Numb triggers its dissociation from the plasma membrane, thereby promoting myosin I–dependent membrane-to-cortex adhesion. This process is essential for plasma membrane retraction in the context of mitotic cell rounding.

Okada et al. show that Bni5 interacts with septin filaments, septin-associated kinase, and myosin-II to regulate septin hourglass architecture and remodeling, retrograde actin flow, and cytokinesis, establishing Bni5 as a key linker and regulator of septins and myosin-II at the division site.

Centrosome stability is essential for spindle bipolarity. Schreiner et al. show that CDK-1 primes PCMD-1 for PLK-1 phosphorylation. Mutations in PLK-1 docking sites impair SPD-5 binding, destabilize the PCM, and delay centriole separation. Schreiner et al. propose that PCMD-1 initiates ordered PCM assembly, ensuring scaffold integrity and function.

Calvo et al. describe a new bioluminescent sensor for measuring luminal Ca2+ in a mildly acidic subcompartment of the endo-lysosomal system. This Ca2+ store accumulates high Ca2+ content via active uptake and releases it via endogenous IP3 receptors with responses comparable to those activated by TPCs and TRPMLs.

The authors demonstrate that B4GALT1 and WLS cooperate to retain the canonical Wnt receptor LRP5/6 on the Golgi apparatus, leading to specific inhibition of the Wnt/beta-catenin signaling in such Wnt-receiving cells that have no expression of Wnt proteins.

Toxoplasma gondii tepsin (TgTEP) interacts with the AP4 adaptor complex and clathrin to mediate actin- and myosin F–dependent vesicle trafficking from the trans-Golgi to the parasite’s lysosome-like PLVAC, highlighting a conserved but repurposed membrane trafficking pathway in Apicomplexa.

Cubillán-Marín et al. find that the vesicle adaptors AP-1, AP-3, and AP-4 are all important for the survival of malaria blood-stage parasites and that these adaptors show an unexpected degree of similarity but also surprising differences to the configuration of the vesicle adaptor machinery in model organisms.

Wang et al. identify Irg1l as a regulator of zebrafish neuromast size. They demonstrate that the Irg1l/itaconate axis promotes supporting cell proliferation by inducing metabolic reprogramming that activates Yap signaling, revealing a previously unrecognized role of metabolites in controlling organ size and sensory function.

Magliozzi and colleagues report that Aip5 and Bud6 directly interact to form a novel “composite” actin nucleator, used to assemble thick actin cables that direct intracellular transport. After nucleation, Aip5 remains bound to the pointed end of the filament, streaming from inward from the cell cortex with actin cable retrograde flow.

Ho et al. identified a novel role of coronin 1A in neuronal development. They find coronin 1A mediates growth cone and filopodial dynamics, and its interaction with E3 ubiquitin ligase TRIM67 is required for morphological responses to the guidance cue netrin-1.

This study defines the native dynamics of the ESCRT-III component Ist1 in mammalian cells, highlighting the existence of multiple, unique pools at endosomes. Growth factor stimulation alters the dynamics of both pools, ultimately facilitating the rapid downregulation of growth factor signaling.

Jensen et al. reveal that the IDR of Canoe is critical for its role in linking cell–cell adherens junctions to the cytoskeleton. Surprisingly, deleting the proximal IDR relocalizes the protein from junctions to nuclei. No IDR subregion is essential for viability. Instead, stickers and spacers act combinatorially to ensure localization, mechanosensing, and function.

Liu et al. show that the transcriptional regulator RTF1 promotes circadian rhythm by enhancing CLOCK occupancy and H3K4me3 deposition at pacemaker gene loci. Their findings reveal a conserved mechanism across species, linking chromatin modification and transcriptional activation to circadian clock control.

Miller et al. demonstrate that the CD47 signaling pathway prevents phagocytosis through dephosphorylation of the Rac GEF Vav. Cancer cells and synthetic targets with CD47 can still be phagocytosed less efficiently through a Rho-dependent mechanism.

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