Issues

Cook et al. show that macrophages sense cell volume disruption as a danger signal promoting transcriptional reprogramming and inflammatory responses via type I interferon signaling. Cell swelling synergizes with pathogen-sensing pathways to amplify inflammation, and macrophage volume regulation coordinates inflammatory responses during influenza infection and influences the development of the cytokine storm.

Newly synthesized cholesterol is transported from the endoplasmic reticulum to the plasma membrane via specialized COPII-independent vesicles. This process requires ceramide for vesicle formation, caveolin proteins as the vesicle coat, and actin-based motors for delivery, revealing a major cellular pathway for cholesterol distribution.

Mayo et al. detail a new mechanism by which the morphogenic regulator Scrib directly organizes cortical actomyosin architecture and dynamics to regulate endothelial adherens junctions and ensure nascent sprout integrity during angiogenesis.

Chen et al. establish a rosette-forming intermediate stem cell model that captures the peri-implantation transition. It reveals a bistable regulatory circuit where OTX2/ID1 synergy maintains pluripotency plasticity under MEK inhibition, thereby bridging a key gap in modeling the progression from naïve to formative states.

To find mating partners, yeast cells use a default polarity site to assemble a GTM, which then redistributes up the pheromone gradient. Here, Pai et al. show that GTM redistribution requires the plasma membrane lipid, phosphatidylserine.

Wang et al. show that migrasome formation requires tetraspanin 4 palmitoylation regulated by DHHC6 and PPT1. This modification drives tetraspanin 4 clustering with cholesterol to build migrasomes. A palmitoylation-deficient tetraspanin 4 mutant (6CA) acts as a dominant-negative tool, blocking migrasome formation and causing developmental defects in zebrafish embryos, establishing palmitoylation as a key regulator of this process.

Zhao et al. reveal that PI(3)P-dependent recruitment of FGD at endosome–mitochondrion contacts activates CDC42 to regulate mitochondrial networks through the actin organization and DRP-1 in Caenorhabditis elegans.

This study identifies a stress-responsive axis composed of HSF2 and HSP110 that preserves genome stability after x-irradiation. By safeguarding RNA polymerase II activity and the transcriptional output of DNA repair genes, this axis prevents replication stress and subsequent lymphoma development, highlighting a potential molecular target for clinical radiosensitization.

Wang et al. develop a high-resolution, long-term live-cell imaging platform in Neurospora crassa to visualize circadian clock proteins expressed at endogenous levels. They show distinct dynamic WCC and FRQ nuclear bodies, FRQ oscillations synchronized among nuclei, and internuclear protein exchange, revealing how subcellular organization and internuclear communication coordinate timing in a multinucleated syncytium.

Krahn et al. use budding yeast to examine membrane recycling at the Golgi apparatus. They describe an in vivo vesicle capture assay that reveals which resident Golgi proteins recycle together in the same vesicles. The results point to a second COPI-dependent intra-Golgi recycling pathway that operates downstream of the previously described COPI-dependent pathway.

Fan and Yang et al. reveal that the SWR1 chromatin remodeling complex plays a crucial, noncanonical role in preventing the vacuolar delivery of autophagy-related proteins in yeast. This work uncovers a novel link between chromatin remodeling and autophagy dynamics, highlighting the importance of the Atg21-Rvb1 module in this process.

Apical–basal polarity is regulated by conserved cortical proteins, but their requirements vary between organisms. Here, we show that LGL-1 and the RhoGAP PAC-1 redundantly control polarization in the Caenorhabditis elegans embryonic epidermis, providing new insights into how conserved mechanisms are adapted across species.

As budding yeast enter starvation-induced quiescence, respiration is required to properly modulate the biophysics of the cytoplasm and ensure cell survival. Kronig et al. show that a preparatory stress treatment can bypass this requirement for respiration. Preemptive activation of the environmental stress response modulates cytoplasmic diffusion and is sufficient for long-term survival.

This study reveals that cells in moving tissues strengthen their connections by actively shuttling adhesion proteins along cell edges to vertices, enabling rapid responses to mechanical forces. This transport depends on proteins existing in an optimal physical state, like damp sand, that can be modulated by physiological temperature changes, offering new insights into how tissues maintain integrity during development.

Lycas et al. develop a cryo-CLEM workflow to characterize the ultrastructure of dopaminergic varicosities. They resolve in situ structures of TRiC/CCT and the V-ATPase and show that pharmacological activation and inhibition bidirectionally change vesicle density and mitochondrial calcium phosphate content, establishing these as organelle-level markers of dopaminergic neuronal activity.

Park et al. present the crystal structure of an RPGR–TTLL5 co-complex, which reveals TTLL recognition paradigms for non-tubulin substrates and sheds light on disease mechanism for retinal dystrophies caused by TTLL5 and RPGR mutations.

Marescal et al. show that quiescent cells disassemble their centromeres through the transcriptional downregulation of most centromere proteins while preserving those required to maintain centromere identity. During quiescence exit, the centromere is reassembled during S phase, but CENP-A is only redeposited in the following G1 after mitotic exit.

Yang et al. perform a family-wide analysis of RhoGAP and RhoGEF localization and function during Drosophila border cell migration and identify RhoGAP15B as a key regulator of actomyosin dynamics. By limiting RhoA–myosin contractility in leading cells, RhoGAP15B stabilizes protrusions and coordinates cytoskeletal dynamics for efficient collective migration.

Park et al. describe problems that plague the analysis of ribosome specialization, as well as ways to address them to guide experimentation in the field.

Huveneers highlights recent work from Mayo et al. identifying Scribble as a regulator of endothelial adherens junctions during angiogenesis.

Hegde and Germain discuss work from Zhao et al. that establishes a direct link between PI(3)P and actin in mitochondrial dynamics.

Jiarui Jiang and Katheryn E. Rothenberg highlight work from Zheng and colleagues that elucidates how adhesion proteins are rapidly moved along the cell edge to vertices in response to mechanical forces.

Coveney, Hong, and Crosby preview work from the Dunlap lab, which reveals how circadian rhythms are coordinated in a syncytial fungus.