ON THE COVER
Scanning electron microscopy micrograph of ependymal cells lining the surface of a mouse brain ventricle. Motile cilia of ependymal cells protrude into the ventricular space, contacting the cerebrospinal fluid. Image © Ignatenko et al., 2022 https://doi.org/10.1083/jcb.202203019
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Liquid–liquid phase separation drives herpesvirus assembly in the cytoplasm
Moon Jung Song and colleagues preview work by Zhou et al. that describes how the γ-herpesvirus MHV-68 utilizes LLPS in cytoplasmic virion assembly compartment (cVAC) formation.
Cilia bent out of shape over dysfunctional astrocyte mitochondria
Bear and Caspary highlight a study from Ignatenko et al., which reveals that mitochondrial dysfunction leads to abnormal cilia structure and upregulation of motile cilia genes in astrocytes.
Dendrite remodeling according to GARP
Shin and Grueber highlight work of the Jan lab that implicates the GARP complex in sterol transport during dendrite development.
Clipping EpCAM to release Claudin-7 for the greater good of the epithelial barrier
Maintenance of epithelial barrier function requires dynamic repair and remodeling of tight junctions. In this issue, Higashi et al. demonstrate that the proteolytic cleavage of EpCAM by membrane-anchored serine proteinases releases Claudin-7 to join tight junctions, suggesting a novel mechanism that couples sensing with repair of damaged tight junctions.
REC drives recombination to repair double-strand breaks in animal mtDNA
Klucnika et al. find that the DNA helicase REC repairs mitochondrial DNA (mtDNA) by homologous recombination and prevents age-associated mtDNA mutations. This study provides the first insight into the molecular machinery of mtDNA recombination in animals and demonstrates its importance in safeguarding the mitochondrial genome during ageing.
Liquid–liquid phase separation mediates the formation of herpesvirus assembly compartments
A mature herpesvirion contains dozens of structural proteins, whose assembly in the vast cytosolic space is a daunting task. Zhou et al. uncovered liquid–liquid phase separation as a strategy to form cytoplasmic virion assembly compartments, mediated by a viral tegument protein, to facilitate virus assembly.
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes
Various types of mitochondrial dysfunction cause neurodegeneration, but how these defects affect neural cell types is poorly understood. Here, the authors show that mitochondrial DNA depletion in astrocytes causes abnormal primary cilia morphology with aberrant induction of motile cilia factors.
ATM inhibition drives metabolic adaptation via induction of macropinocytosis
Huang and Chen et al. find that inhibition of ATM in cancer cells induces uptake of branched-chain amino acids via macropinocytosis. This work also reveals that macropinocytosis is a metabolic vulnerability of cancer cells treated with ATM inhibitors.
APC/CCdc20-mediated degradation of Clb4 prompts astral microtubule stabilization at anaphase onset
Zucca et al. identify in budding yeast two evolutionary conserved mitotic machineries, the Clb4-CDK1 and APC/CCdc20 complexes, as central regulators of astral microtubule dynamics.
Signal sequences encode information for protein folding in the endoplasmic reticulum
Sun et al. show that proteins with marginally hydrophobic signal sequences pause at the Sec61 translocon on their way into the ER and require Sec63/BiP to overcome the pause and facilitate subsequent protein folding in the ER, which prevents protein aggregation during BiP deficiency.
Convergence of secretory, endosomal, and autophagic routes in trans-Golgi–associated lysosomes
Zhou et al. document that the vicinity of the trans-Golgi is the main location for lysosomes in Drosophila cells. They also show that the trans-Golgi–associated degradative compartment, where basal microautophagy of secretory cargos normally takes place, additionally contributes to autophagic vesicle formation under stress conditions.
RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes
Sorting luminal lysosomal hydrolases from Golgi requires the retrieval and efficient transport of their receptor CI-M6PR from endosomes to the trans-Golgi network (TGN). Rawat et al. demonstrate that Rab14 and Arl8b recruit RUFY1 to mediate dynein-dependent retrograde transport of CI-M6PR endosomes to the TGN.
The GARP complex prevents sterol accumulation at the trans-Golgi network during dendrite remodeling
O’Brien et al. show that both the GARP and EARP complexes regulate dendrite development. Sterol accumulates specifically in GARPKO neurons at the trans-Golgi. Targeting Osbp rescues sterol accumulation, Golgi morphology, and adult dendrite growth, implicating sterol transport in dendrite development.
V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans
Stressed mitochondria activate the mitochondrial unfolded protein response (UPRmt) to improve organismal health. Li et al. show that increased ATFS-1 translation, mediated by v-ATPase/TORC1 and involving multiple cellular organelles including lysosomes and ribosomes, plays an essential role in UPRmt activation and mild mitochondrial stress-induced longevity.
The Cdc42 GAP Rga6 promotes monopolar outgrowth of spores
Wenfan Wei and Biyu Zheng et al. report the crucial role of the Cdc42 GTPase-activating protein in dictating the monopolar growth of spores and demonstrate that the specific function of Rga6 depends on its characteristic localization on the plasma membrane.
β-heavy-spectrin stabilizes the constricting contractile ring during cytokinesis
Silva et al. show that plastin/PLST-1 and the β-heavy-spectrin/SMA-1 make distinct contributions to constriction of the cytokinetic contractile ring: PLST-1 promotes F-actin connectivity at the cell cortex and cortical tension that counteracts ring constriction, while β-heavy-spectrin protects fragile rings from ruptures and facilitates ring repair.
The β-cell primary cilium is an autonomous Ca2+ compartment for paracrine GABA signaling
Sanchez, Incedal et al. identify a mechanism that enables excitable cells to utilize Ca2+ in a cilia-autonomous manner. This mechanism allows cilia to sense GABA and initiate cilia-specific Ca2+ signaling through cilia-localized GABAB1 receptors.
Glial TGFβ activity promotes neuron survival in peripheral nerves
Axon maintenance is critical to sustaining a functional nervous system as animals age. Glia contribute to axon maintenance, but precisely how is not well characterized. This work identifies a battery of glial genes that regulate axon support. These genes provide insight into in vivo mechanisms of axon maintenance and may help explain how glial dysfunction leads to neurodegeneration.
EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier
Higashi et al. discover a proteolysis-based maintenance mechanism for the epithelial tight junction (TJ) barrier. They show that breaks in TJs locally induce the cleavage of basolateral EpCAM by apical membrane-anchored serine proteinases, which release claudin-7 from EpCAM and repair the breaks.
Hemicentin-mediated type IV collagen assembly strengthens juxtaposed basement membrane linkage
Tissue attachment through linking juxtaposed basement membranes (BMs) is crucial for the structure and function of many organs. Gianakas et al. identify a key role for hemicentin and fibulin-1 in initiating BM–BM attachment and type IV collagen in stabilizing this linkage and allowing it to resist high mechanical loads.
Force tuning through regulation of clathrin-dependent integrin endocytosis
ICAP-1 controls integrin endocytosis through interacting with NME2, a key regulator of dynamin-dependent clathrin-coated pits fission. Control of clathrin-mediated integrin endocytosis by an integrin inhibitor is an unprecedented mechanism to finely tune physical forces at focal adhesions.
Real-time imaging of RNA polymerase I activity in living human cells
Fu et al. develop a new tool for real-time monitoring of ribosomal RNA synthesis in living cells. This technology can be used to quantitatively measure RNA polymerase I (Pol I) transcriptional activity under various conditions, which facilitates large-scale screening of Pol I regulators.