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Cover Image
ON THE COVER
Confocal image of migrating mouse fibroblast L929 cell overexpressing GFP-RTN4C, stained with Wheat Germ Agglutinin (WGA; cyan) to visualize the plasma membrane, retraction fibers (RFs), and migrasomes. Tubular ER is labeled by GFP-RTN4C (yellow). The image illustrates that migrasomes grow at the tips or intersections of RFs during cell migration. Meanwhile, tubular ER attaches to migrasome initiation sites to extend into RFs and migrasomes, establishing localization within RFs and migrasomes, facilitating spatially encoded signal transmission coupling cell migration. Image © Fan et al., 2025 https://doi.org/10.1083/jcb.202505064 - PDF Icon PDF LinkTable of Contents
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Spotlights
Multifaceted “composite” actin nucleator orchestrates polymerization via dynamic assembly
Han and Miao highlight recent findings from Magliozzi et al. identifying a novel “composite” actin nucleator for the assembly of thick actin cables.
Sensing danger at the bridge
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.
A new probe illuminates endo-lysosomal Ca2+ measurements: A role for vesicular IP3 receptors?
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
Reevaluating the roles of PPARs and nuclear receptors in human peroxisome biology
Mast et al. challenge the PPAR paradigm and show human peroxisomes expand via hominid-specific pathways that link specialization to immunometabolic functions.
Reports
Phosphoproteomic identification of Mos–MAPK targets in meiotic cell cycle and asymmetric oocyte divisions
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.
Contact-dependent incorporation of endoplasmic reticulum into retraction fibers and migrasomes
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.
Tubulin regulates stability and localization of STMN2 by binding preferentially to its soluble form
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
Roles of Srs2/PARI-family DNA helicases in NoCut checkpoint signaling and abscission regulation
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.
IQSEC2/BRAG1 may modulate postsynaptic density assembly through Ca2+-induced phase separation
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.
Adapting plasma membrane for mitotic cell rounding through Aurora A phosphorylation of numb
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.
Bni5 regulates and coordinates septin architecture and myosin-II functions at the cell division site
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.
PCMD-1 stabilizes the PCM scaffold and facilitates centriole separation
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.
Direct measurements of luminal Ca2+ with endo-lysosomal GFP-aequorin reveal functional IP3 receptors
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.
B4GALT1 and Wntless collaborate to block LRP5/6 translocation from Golgi to cell surface
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.
Tepsin and AP4 mediate transport from the trans-Golgi to the plant-like vacuole in toxoplasma
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.
Vesicle adaptors in malaria parasites show conservation and flexibility of protein sorting machinery
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.
Irg1l regulates neuromast size via metabolic reprogramming to promote supporting cell proliferation
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.
Aip5 forms a “composite” actin nucleator with Bud6 and caps pointed ends of actin filaments
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.
Coro1A and TRIM67 collaborate in netrin-dependent neuronal morphogenesis
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.
Analysis of native Ist1 dynamics reveals multiple pools of ESCRT-III on endosomes
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.
A key role of Canoe’s intrinsically disordered region in linking cell junctions to the cytoskeleton
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.
RTF1 enhances CLK occupancy and histone methylation at key circadian clock pacemaker gene loci
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.
CD47 inhibits phagocytosis through Vav dephosphorylation
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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