Issues

Gilk highlights work from Acevedo-Sánchez and colleagues revealing that the cytosolic bacterial pathogen Rickettsia parkerii hijacks host machinery to form stable membrane contact sites with the ER.

Priya Sivaramakrishnan previews work from Lessenger et al., which shows that regulated polyploidy in the C. elegans intestine is important for modulation of transcript levels, cell size, and tissue function.

Velez-Aguilera and Jantsch discuss work from the Dumont lab that utilized sophisticated imaging approaches of Caenorhabditis elegans embryos undergoing meiosis to reveal the existence of a novel double-membrane structure, called the interkinetic envelope, in oocytes during interkinesis.

Lessenger et al. show that developmentally regulated polyploidy in the C. elegans intestine is essential for cell size, production of highly expressed transcripts, tissue function, and organismal fitness. They identify several compensation mechanisms used to buffer mRNA and protein concentration against an artificially generated DNA limitation.

The NSP3/4/12 axis in β-coronaviruses orchestrates the formation of double-membrane vesicles (DMVs) and the assembly of replication organelles by utilizing distinct domains of NSP3 and NSP4. The synthesis of dsRNA cargo by replication–transcription complexes on the exterior of DMVs plays a crucial role in determining DMV size.

Acevedo-Sánchez et al. characterize a novel interkingdom contact site between the ER and a cytosolic bacterial pathogen. They report that these bacteria–ER contacts (BERCs) require the tethering proteins VAPA and VAPB and that actin-based motility of the pathogen negatively impacts the frequency of their formation.

Edington et al. determine that Mdm33 and CCDC51 are functionally conserved mitochondrial inner membrane proteins that are required for normal mitochondrial morphology. The authors show that the proteins spatially demarcate and are required for a subset of mitochondrial division events, suggesting that internal mitochondrial proteins facilitate fission in human cells.

El Mossadeq et al. show that during female meiosis in C. elegans, an interkinetic envelope forms around the segregating chromosomes between meiosis I and II. This unique structure shares features with the nuclear envelope but has a distinct composition, assembly, and function.

The Rho exchange factor ARHGEF17/TEM4 is known to modulate actin cytoskeleton and actin-mediated contractility. Prifti et al. now demonstrate that TEM4 regulates progression though the cell cycle in G1 through regulation of the pro-proliferative transcription factor YAP. The consequences of TEM4 loss and YAP downregulation include severe disruption of many mitotic processes resulting in aberrant chromosome segregation.

Liang et al. elucidate that TPX2 possesses α-helical repeats exhibiting opposite preferences for “extended” and “compacted” tubulin dimer spacing, with the C-terminal repeat group R8-9 being crucial for its function. They also highlight the synergy between TPX2 and HURP in stabilizing spindle microtubules.

Using quantitative and super-resolution microscopy of loop extruders and DNA, Brunner et al. show that the interphase Cohesins form chromatin loops in a sequential and hierarchical manner, which is conceptually very similar to Condensins generating DNA loops during mitosis.

This study uncovers a key regulatory mechanism by which Polo-like kinases control the assembly and disassembly of the synaptonemal complex during C. elegans meiosis. Localized phosphorylation of SYP-5 and SYP-6 enables their electrostatic interactions with chromosome axes, thereby linking synapsis initiation to homologous chromosome pairing.

This paper shows how epithelial cell–cell junctions play a critical role in the fidelity of cell division, where persistent unfolding of the mechanosensitive cadherin complex and actin-binding component, alpha catenin, interferes with cytokinesis through excessive sequestration of the abscission factor, LZTS2.

Sainz et al. investigate mitochondrial respiration-independent signaling induced by acute mtDNA depletion and uncover a role for FAM43A in a CHK2-dependent mitochondrial stress signaling pathway. FAM43A is upregulated in response to mtDNA depletion and performs a checkpoint-like function to limit mitochondrial biogenesis and turnover during mtDNA stress.

Holmes and colleagues show that AKT activation is blocked by commonly used PIP₃ biosensors, but that this can be overcome by expressing biosensors at single-molecule levels—which also improves kinetic fidelity and sensitivity.

Haploinsufficiency of DBA causative ribosomal protein genes caused significant mitochondrial morphological changes; only loss of rps-10 led to mitochondrial dysfunction—including reduced oxygen consumption, energy levels, and mitochondrial activity. These findings suggest a conserved mechanism linking ribosomal stress to mitochondrial function via altered mitochondrial translation.

Iyer et al. combine in vitro reconstitution assays with cryo-electron tomography, biophysical, and cell biological approaches to show that two centriolar proteins, CP110 and CPAP, exhibit antagonistic activities at microtubule plus ends. Together, they impart very slow but processive microtubule polymerization, and their interaction promotes robust centriole formation.

Thomas and Moore show that budding yeast kinesin-5 motors exhibit selective sensitivity to the β-tubulin carboxy-terminal tail. The results suggest a general mechanism for how tubulin code may be functionally read and used to modulate the activity of different kinesins.

Baum and Nguyen et al. ask how the Connexin43 gap junction channel knows how to arrive at its correct plasma membrane subdomain. They find Connexin43 mRNA encodes a truncated isoform that caps actin and patterns the microtubule-based delivery apparatus for targeted delivery of full-length channels.

This study reveals that MYO18B, an unconventional myosin II, positively regulates lysosomal exocytosis by promoting focal adhesion maturation. Lysosomal exocytosis occurs in the vicinity of focal adhesion, prompting an unexpected interplay between lysosomal activities and cellular mechanosensing.

The accumulation of defective polypeptides is a significant cause of various diseases. The authors developed a probe that is specific for defective proteins, which allowed the isolation and visualization of as-yet-hypothetical existence of endogenous orphaned polypeptides as tangible entities.