Issues

Paumier, Sauvanet, and Gigant highlight work from Muñoz-Hernández, Xu, and colleagues, which describes new insight into the means by which NEDD1 protein recruits the γ-TuRC to microtubule-organizing centers.

Mandal and Kumari highlight recent work from Aceitón and colleagues, describing mechanisms underlying the effect of mechanotransduction in B cells on antigen extraction and presentation at the immune synapse.

Zhang and Ding discuss recent work from Sen et al. describing how ethanol impairs hepatocyte lipid droplet breakdown via a novel UBXD8-p97/VCP-HSD17β13 axis.

Powell and Ables preview work from Ghosh et al., which reveals that ecdysone signaling reprograms epithelial follicle cells toward a phagocytic fate during late oogenesis.

Morgan discusses how progress in cell biology is hindered by significance testing and the need for a shift to effect size estimation.

North et al. highlight emerging evidence that LIRs act as protein interaction hotspots, coordinating diverse protein–protein interactions across the autophagy pathway.

Cantwell et al. utilize Ciona and Xenopus systems to uncover conserved differential CK2 regulation of the RanGTP pathway of spindle assembly in meiosis and mitosis, contributing to the rapid, dramatic change in spindle morphology seen at the meiosis-to-mitosis transition in very early embryogenesis.

The γ-TuRC is recruited to microtubule-organizing centers by NEDD1. Muñoz-Hernández et al. report cryo-EM structures revealing how NEDD1’s C terminus forms an α-helical tetramer that docks onto the γ-TuRC without inducing major conformational changes in the complex, compatible with CDK5RAP2 binding and γ-tubulin ring closure.

Ethanol consumption contributes to hepatic steatosis by unknown mechanisms. We found the association of a lipid droplet protein segregase ATPase, VCP/p97, is markedly reduced in EtOH-damaged hepatocytes, preventing the targeting of a key LD enzyme HSD17β13 to the lysosome, leading to an increase in hepatocellular LD content.

Basello et al. investigate the molecular principles governing the formation of nuclear Cajal bodies. They show that coilin oligomerization and its interactions with RNA and snRNPs are essential for Cajal body integrity and propose a mathematical model describing Cajal body dynamics.

Stu2 displays dynamic localization patterns in the cell cycle, with different kinetochore and microtubule distributions during distinct phases. Phosphorylation near Stu2’s C-terminus reduces its attachment to kinetochores to promote its microtubule activity in anaphase. Cdc5 and PP2A^Cdc55 play counteracting roles in this pathway to promote proper timing of Stu2 phosphorylation.

Studies described in this manuscript show that cyclin N-terminal domain containing 1 (CNTD1) is a critical regulator of crossover formation during prophase I of meiosis in females. Loss of CNTD1 results in severe depletion of oocytes at birth leading to loss of the ovarian reserve.

Lipid synthesis supports membrane growth and organelle biogenesis. Hwang et al. show that synthesis of sphingolipids, mainly long-chain bases, is essential to increasing nuclear membranes during cell division. Failure to make sphingolipids in human cells causes abnormal nuclear morphology and genomic instability.

Centriolar satellites are cytoplasmic particles found concentrated near centrosomes and the base of cilia in vertebrate cells whose functional contribution has long been unclear. Here, Pachinger et al. present a model for satellites not as transport modules but as sites of translation specifically of centrosomal and ciliary proteins.

Martinez et al. identify that the RNA-binding protein, UNK, facilitates PLK4-induced centriole overduplication and promotes centriole and centriolar satellite protein localization. Protein synthesis levels at centrosomes are temporally controlled upon PLK4 expression, and UNK and CEP131 promote translation at centrosomes during centriole overduplication.

The E3 ligase Parkin ubiquitinates many proteins. Koszela et al. identify and biochemically validate a direct Parkin interaction with a substrate, Miro1. The results explain fast kinetics of Miro1 ubiquitination by Parkin in recombinant assays and provide a molecular basis for previous observations of Miro1-dependent Parkin recruitment to mitochondrial membrane.

Although DJ-1/PARK7 has been reported to function as a cPGA hydrolase, the molecular mechanisms have yet to be fully elucidated. In this study, the authors combine in silico molecular modeling with cell-free experimental analyses of DJ-1 mutants and present an evidence-based mechanism for DJ-1–mediated cPGA hydrolysis and its pathophysiological significance.

This study shows that the combination of hypoxia and acidosis, common in tumors, produces only transient activation of HIF-1α activity due to its autophagic degradation. Consequently, key HIF targets are not induced, helping prevent excessive acidification by fermentation. This pH-hypoxia interplay has implications for cancer diagnostics, treatment, and experimental design.

B cells sense mechanical cues at the immune synapse and respond by remodeling their intracellular architecture. ATAT1-dependent microtubule acetylation drives this process by coordinating cytoskeletal dynamics and lysosome positioning, which enhances antigen extraction and presentation, uncovering a mechanotransduction pathway that fine-tunes adaptive immune responses.

We elucidate the role of ecdysone signaling in orchestrating the removal of nurse cells by transforming the epithelial follicle cells to phagocytic fate during late oogenesis. Our data provide unprecedented novel molecular insights into how ecdysone signaling reprograms epithelial follicle cells toward a phagocytic fate.

Belyantseva and Liu report that taperin encircles and stabilizes F-actin at auditory hair cell stereocilia bases and bundles F-actin. Taperin deficiency causes stereocilia disassembly, rootlet breakage at pivots, and other abnormalities culminating in deafness. Thus, taperin bundles F-actin to maintain rootlet integrity and lifelong hearing.

Breast cancer cells isolated from lung micrometastases have altered metabolism, which influences extracellular vesicle production to generate invasive microenvironments.

Yadav & Jadhav et al. present the design, synthesis, and validation of a novel cell-permeable biotin-HaloTag ligand. The reported ligand expands the HaloTag toolbox by enabling in vivo labeling and providing capabilities for efficient affinity capture of protein variants from live cells.