Issues
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ON THE COVER
Scanning electron microscopy image of a human osteoclast derived from blood monocytes on bone slices. The osteoclast is degrading the bone matrix as revealed by the holes in the bone. Image © Ophélie Dufrançais and Renaud Poincloux, 2025 https://doi.org/10.1083/jcb.202409169 - PDF Icon PDF LinkTable of Contents
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Spotlights
Slowing down to take it in: Endocytosis during cellular aging
Prosser highlights work from Antenor and colleagues, describing how elevated vacuolar pH in aging yeast cells slows clathrin-mediated endocytosis.
A pyrophosphatase that regulates lipid precursors of N-glycosylation
Menon discusses recent advances by Li et al., identifying a DLO-pyrophosphatase (Llp1), which maintains DLO quality control in eukaryotes.
Moesin strikes an “Actin”g balance to regulate osteoclast fusion and activity
Marwa Zeyad and Yousef Abu-Amer highlight work from Dufrancais et al., which reveals a role of tunneling nanotubes in moesin-mediated osteoclast fusion and regulation of osteoclastogenesis.
Beyond selection: How chromosome 12 gain dominates stem cell genomes
Benamozig and Shoshani highlight work from the Gorbsky Lab, which shows how chromosomal instability can rapidly cause aneuploidy.
Perspectives
Patterning in motion: Cell interfaces guide mesenchymal collective migration and morphogenesis
Bischoff and Mayor present a framework for comparing mesenchymal collective migration modes and explain their roles in patterning and morphogenesis.
Understanding microtubule dynamics: The synergy of technology, theory, and experiment
The history of research on microtubule polymerization is described in terms of the ideas, technologies, and observations that have emerged as countless researchers have studied the dynamics of these essential cytoskeletal polymers.
Reports
Origin of chromosome 12 trisomy surge in human induced pluripotent stem cells
Narozna et al. reveal that trisomy 12 arises en masse during crucial passages of iPSCs. The short p arms whose ends are eroded by replication stress trigger p-arm chromosome bridges at anaphase leading to chromosome mis-segregation, formation of micronuclei, and trisomy. A slight growth advantage allows trisomic cells to persist and eventually dominate.
Articles
Mechanisms of nuclear segregation in a multinucleate multibudding yeast
The multinucleate, multibudding yeast, Aureobasidium pullulans, delivers nuclei into each daughter bud during mitosis. Here, we image microtubules during mitosis, revealing mechanisms ensuring that most daughters inherit one and only one nucleus.
Allocation of resources among multiple daughter cells
Cell division commonly produces two daughter cells, but sometimes large cells produce multiple daughters. Here, we address how mothers partition growth equally among their buds in the multi-budding yeast Aureobasidium pullulans. Even partitioning stems directly from effective equalization of polarity sites.
Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity
Galectin-9 is a critical regulator of dendritic cell basal and chemokine-driven migration by organizing CD44 at the cell surface and promoting RhoA-GEF-H1–mediated signaling. Galectin-9 rescued the motility of tumor-immunocompromised dendritic cells, validating the physiological relevance of our data and underscoring its implications for DC-based immunotherapies.
LLP1 is a pyrophosphatase involved in homeostasis/quality control of dolichol-linked oligosaccharide
Dolichol-linked oligosaccharide (DLO) is the precursor for asparagine-linked protein glycosylation. We identified a DLO-pyrophosphatase (Llp1), which is involved in DLO homeostasis/quality control. We provide insights into how the cellular levels and quality of DLOs are maintained in eukaryotes.
Multiple interactions recruit BLTP2 to ER-PM contacts to control plasma membrane dynamics
Dai et al. report the localization of BLTP2 in different human cell types and reveal binding partners that mediate its tethering to the PM and to PM-connected structures, including tubular recycling endosomes and recycling macropinosomes undergoing fusion with the PM.
SCFFBXO21-mediated ubiquitination and degradation of NMNAT2 regulates axon survival in nerve injury
In this study, Long et al. identify NMNAT2 as a bona fide substrate of an SCFFBXO21 E3 ligase complex that ubiquitinates NMNAT2 at K155 and promotes its turnover in neurons and reveal that Fbxo21 deficiency confers axonal protection both in vitro and in vivo.
JIP4 and RILPL1 utilize opposing motor force to dynamically regulate lysosomal tubulation
As a response to membrane damage, lysosomes can generate tubules sorted into mobile vesicles in a process called LYTL. This new study shows how two distinct pRAB effectors and RHD members, JIP4 and RILPL1, provide antagonistic motor force to regulate the dynamics of LYTL tubules.
PEX14 acts as a molecular link between optineurin and the autophagic machinery to induce pexophagy
This study uncovers and defines the peroxisomal membrane protein PEX14 as a key player in optineurin-driven pexophagy, advancing our mechanistic understanding of this cellular process. These findings open new avenues for developing therapeutic strategies targeting diseases associated with defective pexophagy.
Moesin controls cell–cell fusion and osteoclast function
Dufrançais et al. show that moesin, a member of the ERM proteins, plays a negative regulatory role in osteoclastogenesis. We unravel the importance of tunneling nanotubes in moesin-mediated osteoclast fusion and the involvement of the β3-integrin/RhoA/SLK pathway. Moesin-deficient mice are osteopenic with increased osteoclast activity.
Vacuolar pH regulates clathrin-mediated endocytosis through TORC1 signaling during replicative aging
Clathrin-mediated endocytosis becomes less efficient in aging yeast mother cells due to changes in vacuolar pH. This change alters TORC1-Npr1 signaling and slows endocytic dynamics. Restoring vacuolar acidity or modulating TORC1-Npr1 signaling preserves endocytosis, which may help maintain cellular function in aging cells.
Target cell adhesion limits macrophage phagocytosis and promotes trogocytosis
Macrophages are presumed to attack antibody-opsonized cancer cells by phagocytosis. Rollins et al. found that macrophages attack adherent cells using trogocytosis, or cell nibbling, instead of phagocytosis. Reducing target cell adhesion increased phagocytosis. Mitotic cells, which naturally disassemble adhesions, were more vulnerable to phagocytosis.
PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity
Rivero-Ríos et al. demonstrate that dynamic PI(3)P synthesis at postsynaptic sites regulates synaptic plasticity. The authors show that PI(3)P drives the recruitment of SNX17 and SNX27 to synapses to promote the recycling of cell surface proteins necessary for long-term potentiation.
Tools
ReSCU-Nets: Recurrent U-Nets for segmentation of three-dimensional microscopy data
Hawkins et al. introduce ReSCU-Nets, recurrent neural networks for integrated segmentation and tracking of three-dimensional microscopy images. ReSCU-Nets outperform state-of-the-art image segmentation models and reveal that gap junctions are necessary for the molecular and cellular rearrangements that drive rapid wound healing in embryos.
PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production
Weckerly et al. report a novel biosensor, PILS-Nir1, that detects phosphatidic acid in live cells, revealing the lipid’s dynamics with improved sensitivity and selectivity over existing probes.
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