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Issues

In Memoriam

Laura Feltri (1963–2023) has been a pioneer in the study of extracellular matrix in peripheral nervous system myelination.

Spotlights

Saito and Maeda discuss work by Yang et al. showing that all four p24 subfamilies are required for secretion and their interactions with Tango1 are vital for a stable ER–Golgi interface.

Shiori Sekine and Yusuke Sekine discuss work by Krakowczyk et al., which discovered a new quality control mechanism in human cells that eliminates stalled proteins in the mitochondrial TOM translocase.

Plants execute pivotal growth decisions by changing membrane trafficking of cell wall components. Antonio Galindo highlights new results from Farhah Assaad, Christian Wiese, and colleagues showing how the TRAPPII complex orchestrates growth decisions when resources are limiting.

Reviews

Shi et al. review emerging concepts regarding crosstalk mechanisms of Polycomb repressive complexes and their implications in epigenetic therapies for cancer.

Akizuki et al. review our latest knowledge of the roles of non-canonical ubiquitination in protein stability and signal transduction.

Viewpoint

Sebbagh and Schwartz discuss new research indicating that the nectin/afadin complex is the major force transmitting structure in mature intestinal epithelial adherens junctions.

Reports

Fellows et al. report that individual dynein motors can move the entire axon length during retrograde transport. They find factors LIS1 and NDEL1, needed for transport initiation, also move with cargos. In the anterograde direction, dynein and its cofactor dynactin are transported separately, keeping them apart until required.

Articles

Arends et al. show that DUX4-induced transcription of pericentromeric human satellite II (HSATII) repeats leads to nuclear foci formation of KDM2A/B–PRC1 complexes. Nuclear accumulation of KDM2A/B–PRC1 at HSATII regions impairs PRC1 activity and DNA damage response.

Marquardt et al. show that the septin-associated kinases Elm1 and Gin4 regulate each other via both direct binding and phosphorylation to control septin hourglass assembly and remodeling at different points of the cell cycle in the budding yeast Saccharomyces cerevisiae.

Yang et al. systematically analyze in Drosophila the function of the four p24 protein subfamilies and discover that interaction with Tango1 is essential for their concentration between ER and Golgi and for efficiency of COPII-mediated general secretory transport.

Wiese et al. explore the role of the trans-Golgi network in plant stress responses. They uncover physical and genetic interactions between the Arabidopsis TRAPPII complex and shaggy-like kinases. The findings suggest that shaggy-like kinases mediate plant adaptation to environmental cues by phosphorylating TRAPPII.

Krakowczyk et al. discovered the unique ways human cells handle mitochondrial protein transport failures. They reveal a mechanism, distinct from fungi, where human cells rely on mitochondrial factors to clear blockages. This involves the protease OMA1 and a triggered proteolytic cleavage of the stalled protein.

Xiao et al. conduct an imaging-based screen to uncover regulators of mitochondrial-derived compartment (MDC) biogenesis, from which they identify distinct roles for the phospholipids cardiolipin and phosphatidylethanolamine in MDC formation. Specifically, cardiolipin is required for MDC formation, whereas a decline in phosphatidylethanolamine activates MDC biogenesis.

Sorting of signaling receptors between membrane environments can regulate their activity. Shimizu et al. show that localization of Notch to alternative microdomains on the endosome switches between different mechanisms of activation, and lateral movement of Notch on the endosome membrane between these microdomains is regulated by Deltex and limited by differential roles of ESCRT-I and III complexes.

Using live-cell microscopy, we find that loss of VPS13C in human neurons disrupts lysosomal morphology and dynamics with increased inter-lysosomal tethers, leading to impaired lysosomal motility and defective lysosomal function as well as a decreased phospho-Rab10-mediated lysosomal stress response.

Endoplasmic reticulum homeostasis depends on protein quality control systems such as ER-associated degradation. This work reveals that the complete degradation of a substrate containing a folded domain in the lumen requires coupling between the retrotranslocation and degradation steps and that this is ensured by the membrane protein Dfm1.

Membrane anchors of RAS play major roles in select lipid enrichment of RAS on the plasma membrane. Arora et al. show that the cytoplasmic RAS G-domains fine-tune selectivity of lipids. Their findings provide a mechanism for the allele-specific oncogenesis of KRAS4B.

Tight junction membrane proteins, claudins, JAM, and CAR, coordinately regulate the nanometer-scale organization of ZO-1 molecules and are required for the mechanical resistance of apical junctions in epithelial cells.

In Special Collection: Cellular Neurobiology 2024

Anterograde transport of axonal mitochondria is critical for the maintenance of the mitochondria pool and neuronal health. Wu et al. show that the endogenous kinesin-1 and RIC-7 localize at the leading end of mitochondria to drive axonal anterograde transport in vivo in C. elegans.

Tools

The dynein motor positions many organelles, vesicles, and macromolecules in cells. However, it is unclear how the transport machinery is synthesized, assembled, and regulated. Here, Wong et al. identify many candidate players in dynein-based transport through a genome-wide, high-content arrayed CRISPR screen.

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