Issues

Mara Duncan discusses work from Robinson and colleagues that monitors the entry of newly synthesized and recycled cargo into clathrin-coated vesicles associated with the adaptor protein complex-1.

The slender shape of axons makes them uniquely susceptible to mechanical stress. Leterrier discusses new work from Wang and colleagues finding that transient actomyosin beading protects axons by limiting the spread of damaging calcium waves.

Nabi and colleagues discuss supervision paradigms for biological discovery from super-resolution microscopy to enable AI-accelerated exploration of the nanoscale architecture of subcellular macromolecules and organelles.

Huna et al. provide insights into the shifting perception of cellular senescence: from a mere cell proliferation arrest to a reinforcement or change of cell identity.

Vivek Malhotra discusses our emerging understanding of the roles of COPII in mediating the export of diverse cargoes from the ER.

Zweifach explains how to calculate how many cells to analyze per sample to achieve reasonable statistical power in microscopy experiments.

In human cells, the S-phase-promoting kinase CDC7 exists in two alternative complexes: CDC7-DBF4 or CDC7-DRF1. Here, Göder et al. show that while CDC7’s essential function can be supported by both subunits, DBF4 is the primary mediator of CDC7 activity during DNA replication.

Chong et al. show that chromosomes biorient and correct errors with varying efficiencies. Chromosome size and the spindle forces that scale with size determine error correction efficiency such that elevated tension at kinetochores on long chromosomes allows premature stabilization of non-bioriented attachments, delaying their alignment.

Bagdadi et al. show that, although usually considered inactive, GDP-bound tubulin polymerizes into remarkably stable microtubules. These results reveal that microtubules possess an intrinsic capacity for stability, independent of accessory proteins. This finding provides novel mechanisms to revisit microtubule dynamics.

In budding yeast, the growth of the daughter bud is required for mitotic progression. Analysis of signals that control bud growth suggests that the mitotic exit network (MEN) ensures that mitotic exit occurs only when an appropriate amount of bud growth has occurred.

The authors discovered histone H3K36me2, which is believed to be enriched in potentially active genomic regions, is also located in transcriptionally inactive regions called heterochromatin in some cell types. The detailed molecular mechanism of its heterochromatin targeting is now revealed.

Binucleated polyploid hepatocytes are common in the mammalian liver, but it is unclear how they arise in humans. Darmasaputra et al. investigate how binucleated cells arise in human fetal–derived hepatocyte organoids, demonstrating a late cytokinetic regression during the endomitosis M phase.

Human culture cells are thought to divide symmetrically. This study reveals that centrosome age breaks via the kinase Plk1 the symmetry of spindle size through a differential microtubule nucleation capacity. This asymmetry leads to asymmetric cell divisions giving rise to daughter cells of unequal sizes.

Yeh et al. have revealed the molecular mechanism by which the ribosomal protein uL14 is protected by its dedicated chaperone and the methyltransferase. This dual protection system sequentially delivers uL14, ensuring its quality and safety from the cytoplasm until its incorporation into the pre-60S ribosome.

This study shows that STAU1 condensate recruits and enriches MTOR mRNA to promote mTOR translation. Pathological STAU1 overabundance–induced excessive STAU1 condensate causes mTOR hyperactivation, impaired autophagic pathway, and inefficient clearance of pathogenic protein aggregates, highlighting the importance of balanced phase separation in physiological processes.

Ruehle, Li, and colleagues identify the conserved Poc1 protein to be a triplet microtubule inner junction protein that seals triplet microtubules and supports basal body integrity. Poc1 promotes proximal and core structures that interconnect triplet microtubules and enable forces from beating cilia to be resisted.

In this study, the authors investigate how cells regulate proteasome content in response to catabolic stimuli in vivo. During cellular adaptation to accelerated proteolysis, muscle cells boost proteasome levels by inducing proteasome subunit genes and assembly chaperones in a two-phase transcriptional program that is controlled by multiple transcription factors.

How are mislocalized secretory proteins targeted for destruction? Shimshon, Dahan, et al. discover that DPP8/9 peptidases expose a hidden “destroy me” tag in the targeting signal of substrates upon translocation failure, which flags them for UBR E3 ligases-mediated breakdown, preserving cellular protein balance.

The microtubule-associated cues that underlie the position and traffic of endosomes are poorly understood. Robinson et al. report that endosomes with multivesicular body and late endosome markers localize preferentially to microtubules coated with septins, which promote maturation of CD63 enriched endosomes by hindering their mobility.

Barnaba, Broabent et al. develop K-FOCUS for high-throughput analysis of autophagy foci in human cells and demonstrate that glucose starvation downregulates autophagy via AMP-activated protein kinase, which prevents phagophore tethering to donor membranes to inhibit autophagosome maturation.

The findings reveal how calcium regulates migrasome formation and propose a sequential interaction model involving Syt1 and Tetraspanins in the formation and stabilization of migrasomes. The research uncovers a pivotal step that facilitates the transition from tension-induced swelling to the establishment of a stable migrasome.

Pan et al. found that actomyosin-II–driven reversible beading underpins the resilience of central axons to mild mechanical stress by suppressing the propagation and firing of injurious Ca²⁺ waves. Boosting actomyosin-II activity alleviates axon degeneration in mice with traumatic brain injury.