ON THE COVER
A z-stack projection of spinning disk confocal images showing a C. elegans spermatheca filled with an oocyte. Actomyosin stress fibers (cyan) are labelled with GFP::ACT-1 and the RhoGEF RHGF-1 (magenta) is tagged with tagRFP. Recruitment of RHGF-1 to F-actin is enhanced by tension in the actomyosin network. In turn, RHGF-1 signaling induces contraction, leading to expulsion of the fertilized oocyte from the spermatheca. Image © Avivi Kela et al., 2022 https://doi.org/10.1083/jcb.202203105
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Albert Reynolds (1956–2022): The father of p120
People & Ideas
Chii Jou Chan: The positives of being under "pressure"
Chii Jou Chan investigates how tissue mechanics and fluid pressure regulate mammalian development, with a special focus on folliculogenesis and oocyte quality control.
Mammalian fertilization: Does sperm IZUMO1 mediate fusion as well as adhesion?
Brukman and colleagues provide evidence that the sperm surface protein IZUMO1, which is essential for mammalian fertilization, can induce membrane fusion in cultured cells.
How to unravel a basket: NPC reorganization during meiosis
Veldsink and Veenhoff discuss work from the Ünal lab, which reveals two distinct processes that remodel the nuclear pore complex basket during budding yeast meiosis.
When aging gets on the way of disposal: Senescent cell suppression of efferocytosis
Rothlin and Ghosh preview work from the Murray and El Kasmi labs that identifies a new mechanism by which senescent cells evade their removal by macrophages and block macrophages from eliminating apoptotic corpses.
Pumping up the volume
Catherine Galbraith previews a Tools study from Gallusser and colleagues which describes a new pipeline for training a convolutional neural aimed at rapid automated detection of intracellular structures in volume electron microscopy images.
TIMP-1 is a novel ligand of Amyloid Precursor Protein and triggers a proinflammatory phenotype in human monocytes
The authors identified a new mechanism of monocyte activation that is mediated by the interaction of TIMP-1 with APP. Furthermore, they provide evidence for a TIMP-1-mediated proinflammatory activation of human monocytes in clinical cancer samples.
A novel function for the sperm adhesion protein IZUMO1 in cell–cell fusion
Egg–sperm fusion is the climax of fertilization. In vertebrates, the molecules that directly mediate egg–sperm merger and how this process occurs have been the holy grail of fertilization. Here, Brukman, Nakajima et al. demonstrate that the docking protein IZUMO1 from mouse can merge mammalian cells.
Meiotic nuclear pore complex remodeling provides key insights into nuclear basket organization
King and Wettstein et al. reveal that nuclear pore complexes undergo two distinct remodeling events during budding yeast meiosis: partial and full nuclear basket detachment. In dissecting the regulation of these events, this study provides insights into nuclear basket organization.
α-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity
Lopes et al. perform a pilot dissection of the cancer tubulin code in the NCI-60 cancer cell panel that identifies high α-tubulin acetylation as a biomarker of taxol response and unveils a mechanistic link between α-tubulin detyrosination and the suppression of MCAK activity in taxol-induced cytotoxicity.
VASH1–SVBP and VASH2–SVBP generate different detyrosination profiles on microtubules
VASH1–SVBP and VASH2–SVBP produce global and local detyrosination patterns of microtubule lattices, respectively. These activities rely on the interplay between the N- and C-terminal disordered regions of the VASH enzymes, which determine their differential molecular mechanism of action.
TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1
Autophagy is well known for its anti-inflammatory effects. In this article, Zhou, Rasmussen et al. highlight that selective, autophagy-dependent degradation of the inflammation repressor TNIP1 supports pro-inflammatory gene and protein expression. Similarly as in cancer, autophagy appears to play a dual role in controlling inflammation.
Senescent cells suppress macrophage-mediated corpse removal via upregulation of the CD47-QPCT/L axis
The α-Catenin mechanosensing M region is required for cell adhesion during tissue morphogenesis
Sheppard et al. investigate the role of the α-Catenin M region in epithelial cell adhesion during cell intercalation in Drosophila embryos. The M region regulates mechanosensitive recruitment of Vinculin, Ajuba, and Canoe, with differential recruitment observed at low-, medium-, and high-tension cell contacts, reinforcing adhesion within a cooperative network.
Tension-dependent RHGF-1 recruitment to stress fibers drives robust spermathecal tissue contraction
Avivi Kela et al. discovered a novel mechanotransduction pathway in the C. elegans spermatheca involving tension-dependent localization of a RhoGEF and a positive feedback loop for RHO-1–MyosinII activation that gives an epithelial tube the ability to sense luminal pressure and adjust its contractility in response.
KIF4 regulates neuronal morphology and seizure susceptibility via the PARP1 signaling pathway
Wan et al. reveals the fundamental mechanism of KIF4-regulated chloride homeostasis and neuronal morphology leading to the susceptibility of epilepsy through analyses of mice with mutant found in a patient. This research holds promise for a potential target for treatment.
ARHGAP17 regulates the spatiotemporal activity of Cdc42 at invadopodia
Kreider-Letterman et al. describe a novel mechanism for the regulation of Cdc42 dynamics at invadopodia by the Cdc42-GAP ARHGAP17, which targets to the invadopodia ring during assembly and relocates to the core to inactivate Cdc42 and initiate disassembly.
GSK3α phosphorylates dynamin-2 to promote GLUT4 endocytosis in muscle cells
Laiman et al. discover that GSK3α, but not GSK3β, phosphorylates dynamin-2 to unleash the Bin1 inhibition and promotes GLUT4 endocytosis in skeletal muscle. Importantly, pharmacological inhibition of GSK3α improves insulin sensitivity and glucose tolerance in diet-induced diabetic mice, highlighting GSK3α as a therapeutic target for metabolic disorders.
PI(4,5)P2 diffuses freely in the plasma membrane even within high-density effector protein complexes
Pacheco et al. demonstrate that unbound PI(4,5)P2 diffusion in the PM is rapid and is not slowed by the majority of PI(4,5)P2-dependent PM complexes found there, such as clathrin-coated structures and focal adhesions.
Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion
Combining live TIRF microscopy and fluorescently tagged fibronectin, the authors show that fibronectin secretion by fibroblasts occurs preferentially at leading edge protrusions stabilized by mature focal adhesions and that fibronectin deposition requires both intact microtubules and myosin II contractility.
Follicle cell contact maintains main body axis polarity in the Drosophila melanogaster oocyte
Milas et al. use mechanical and optical perturbation to show the requirement of cell–cell contact between somatic follicle cells and the oocyte in the Drosophila egg chamber for maintaining Par protein polarity and posterior oskar mRNA localization.
ILEE: Algorithms and toolbox for unguided and accurate quantitative analysis of cytoskeletal images
Li and Zhang et al. present Implicit Laplacian of Enhanced Edge (ILEE), an algorithm and toolbox for unbiased, quantitative, and cytoskeletal image analysis. ILEE solves historical challenges and improves the accuracy, stability, and robustness of cytoskeletal quantification, as well as extending the number of quantifiable cytoskeletal features.
Deep neural network automated segmentation of cellular structures in volume electron microscopy
Gallusser et al. present a new pipeline to train a convolutional neural network for rapid and efficient automated detection of intracellular structures of wide range in size and complexity imaged by volume electron microscopy.