Issues
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Cover Image
Cover Image
ON THE COVER
STED microscopy image of myosin IIA (green) and ZO-1 (magenta) of claudin/JAM-A KO MDCK II cells. ZO-1 staining forms a continuous network in control cells. When tight junction membrane proteins are deleted, breakage of the junctions are visible, accompanied with the loosening of the circumferential actomyosin bundle. Image © Nguyen et al., 2024 https://doi.org/10.1083/jcb.202307104 - PDF Icon PDF LinkTable of Contents
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In Memoriam
Laura Feltri: Of Schwann cells, matrix, and family
Laura Feltri (1963–2023) has been a pioneer in the study of extracellular matrix in peripheral nervous system myelination.
Spotlights
p24 family Tango(1) at the endoplasmic reticulum exit site to organize cargo exit
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.
OMA1 clears traffic jam in TOM tunnel in mammals
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.
Unveiling the TRAPP: The role of plant TRAPPII in adaptive growth decisions
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
Crosstalk within and beyond the Polycomb repressive system
Shi et al. review emerging concepts regarding crosstalk mechanisms of Polycomb repressive complexes and their implications in epigenetic therapies for cancer.
The emerging roles of non-canonical ubiquitination in proteostasis and beyond
Akizuki et al. review our latest knowledge of the roles of non-canonical ubiquitination in protein stability and signal transduction.
Viewpoint
Afadin–nectin forces its way to the front
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
Dynein and dynactin move long-range but are delivered separately to the axon tip
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
DUX4-induced HSATII transcription causes KDM2A/B–PRC1 nuclear foci and impairs DNA damage response
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.
Reciprocal regulation by Elm1 and Gin4 controls septin hourglass assembly and remodeling
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.
p24–Tango1 interactions ensure ER–Golgi interface stability and efficient transport
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.
Regulation of adaptive growth decisions via phosphorylation of the TRAPPII complex in Arabidopsis
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.
OMA1 protease eliminates arrested protein import intermediates upon mitochondrial depolarization
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.
The phospholipids cardiolipin and phosphatidylethanolamine differentially regulate MDC biogenesis
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.
Alternative mechanisms of Notch activation by partitioning into distinct endosomal domains
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.
VPS13C regulates phospho-Rab10-mediated lysosomal function in human dopaminergic neurons
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.
The derlin Dfm1 couples retrotranslocation of a folded protein domain to its proteasomal degradation
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.
RAS G-domains allosterically contribute to the recognition of lipid headgroups and acyl chains
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 regulate the mechanical resistance of the apical junctional complex
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.
Polarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport
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
Genome-scale requirements for dynein-based transport revealed by a high-content arrayed CRISPR screen
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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