Issues

Nassar and Ferguson discuss work from Kim et al. showing that TMEM63A protects lysosomes from rupture by acting as a pressure relief valve when membrane tension rises and thereby buying time for downstream membrane repair pathways to engage.

Fröhlich discusses two recent studies describing a plasma membrane ER contact site formed by BLTP2 and its adaptor proteins.

Durand highlights recent work from Wang et al., describing how the motor protein Kif19A shapes the tips of fly mechanosensory cilia.

Qian, Niwa, and Nakajima preview work from Rongwen Xi and colleagues, which identifies region-specific transcription factors that regulate enteroendocrine cell morphology and integration into the gut epithelium.

Rogers et al. demonstrate that heat stress triggers nucleolar remodeling in filamentous fungi, enabling segregation of damaged material and selective inheritance of a new nucleolar compartment. This reveals a chaperone-mediated quality control mechanism that preserves nuclear function in highly polarized, multinucleate cells.

Neurons rely on molecular motors to deliver proteins to precise locations. This study shows that kinesin-2 motors form heterogeneous assemblies with distinct cargo preferences. A KIF3B-enriched assembly preferentially associates with TRIM46, suggesting that variation in motor composition contributes to selective transport during neuronal development.

Maintaining lipid bilayer integrity of membrane-bound organelles is essential for their ongoing and compartmentalized biochemical reactions. Kim et al. describe a mechanism for lysosomes to sense and respond to acute increases in their membrane tension by relieving hydrostatic pressure via the outward transport of major osmoticants.

Restrepo Cruz et al. employ super-resolution microscopy and Bayesian analyses to study the molecular interactions between tetraspanin CD82 and EGFR on the plasma membrane. They reveal the tetraspanin scaffold regulates the nanoscale organization of the receptor, modulating receptor multimerization and inhibiting ligand-independent receptor phosphorylation upstream of cellular proliferation.

Cesar and Kim review how the synaptonemal complex assembles and serves as a dynamic signaling platform that coordinates meiotic recombination.

Kinetochore-localized KMN complexes mediate chromosome segregation by attaching chromosomes to spindle microtubules. Cryo-EM, biochemical, and genetic experiments reveal conserved underlying mechanisms of complex assembly, auto-inhibition, and phosphoregulation that ensure precise control of KMN assembly onto centromeres to enable genome division.

Shen et al. demonstrate that LMNA reduction alters peripheral genome organization in human cardiomyocytes through cytoskeletal forces transmitted by the LINC complex. These findings uncover a microtubule-dependent pathway regulating lamina-associated domains and suggest that the cytoskeleton may contribute to early nuclear dysfunction in laminopathies.

Vinayagamurthy et al. reveal TRF2 is integral for NSC identity. Surprisingly, non-telomeric function of TRF2, instead of commonly understood telomere protection by TRF2, is critical for NSCs. Direct association of TRF2 with DNA G-quadruplex motifs in promoters of differentiation-associated genes tightly regulates transcription to suppress neurogenesis.

Zhou, Wang et al. show that induced polyploidy acts as an intrinsic cellular stress that reprograms epithelial cells to promote motility and phagocytic behavior. Through ER stress and ROS–JNK signaling, polyploid cells gain immune-like behaviors in development and cancer, linking increased genome content to invasive and metastatic traits.

Hao et al. report that lipophilic dye octadecyl rhodamine B (R18) is transported to the ER mediated by membrane transfer proteins. Upon autophagy, ER-resident R18 is transferred to the autophagic membrane via Atg2. After termination, R18 is reversed back to the ER, showing that the direction of bridge-type lipid transfer is modulated by metabolic states.

Bridge-like lipid transfer proteins transport lipids at membrane contact sites, but how they are targeted to these sites is not well understood. Dziurdzik, Sridhar et al. identify a conserved adaptor that recruits BLTP2-like proteins to ER–plasma membrane contacts by binding helical projections on their lipid transfer channel to maintain lipid homeostasis.

Stalder and Pereira et al. combine affinity isolation of post-Golgi carriers, mass spectrometry, and a pooled CRISPR-KO screen to uncover new regulators of Golgi-to-plasma membrane transport. They show that a PTPN23-dependent ESCRT pathway is essential for the secretion of membrane and soluble cargoes, including hormones and antibodies, in specialized cells.

The mechanism by which the conserved Ypt1/Rab1 GTPases mediate the beginning of two cellular processes, secretion and autophagy, is unknown. Gyurkovska et al. use in vivo analysis to show that distinct TRAPP complexes activate the yeast Ypt1 in secretion and autophagy.

Wang et al. reveal how nanoscale polarity emerges at mechanosensory ciliary tips. A kinesin-8 motor, Kif19A, drives localized transport that is stabilized by region-specific receptor binding, counteracting rapid diffusion. This coupling of active transport and local retention provides a general mechanism for building specialized cellular nanocompartments.

Whether and how individual cells within a tissue cooperate with each other to respond to cellular stress has remained elusive. Nandakumar et al. show that Drosophila adipocytes transport select subcellular components across intercellular bridges with their neighbors, and that such transport is required for tissue resilience to various stressors.

Fort et al. identify a mechanobiological gate controlling mesoderm identity in human pluripotent stem cells. They show that actomyosin contractility suppresses mesoderm induction by limiting β-catenin signaling, whereas relaxing cellular tension permits differentiation, revealing a tension-dependent step required for lineage commitment.

Yu et al. reveal how regional transcription factors control the morphology of enteroendocrine cells in fruit flies. Their findings demonstrate that a Ptx1-esg-sSJ regulatory axis determines whether enteroendocrine cells integrate into the gut epithelium, thereby influencing their ability to sense dietary nutrients.

Agarwal et al. define the stage-specific gene expression programs of a leader cell that drives collective tissue invasion during organ development. By combining transcriptomics with functional analysis, they identify membrane trafficking as a central regulator of leader cell behavior, providing a valuable resource for studying collective cell migration in vivo.

Deb Roy et al. introduce an optogenetic tool to rapidly induce microtubule acetylation in living cells. The study shows that microtubule acetylation directly triggers release of the RhoGEF GEF-H1 from microtubules, activating actomyosin contractility, promoting focal adhesion maturation, and driving persistent directional cell migration.