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TanGIBLE: A selective probe for evaluating hydrophobicity-exposed defective proteins in live cells
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.
Report
SARS-CoV-2 NSP3/4 control formation of replication organelle and recruitment of RNA polymerase NSP12
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.
Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events
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.
Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output
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.
Rickettsia parkeri forms extensive, stable contacts with the rough endoplasmic reticulum
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.
Article
α-Catenin force-sensitive binding and sequestration of LZTS2 leads to cytokinesis failure
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.
A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43
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.
An interkinetic envelope surrounds chromosomes between meiosis I and II in C. elegans oocytes
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.
Diverse microtubule-binding repeats regulate TPX2 activities at distinct locations within the spindle
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.
Differential impacts of ribosomal protein haploinsufficiency on mitochondrial function
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.
Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails
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.
Quantitative imaging of loop extruders rebuilding interphase genome architecture after mitosis
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.
MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation
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.
Identification of the Polo-like kinase substrate required for homologous synapsis
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.
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