Nucleoporin PNET1 coordinates mitotic nuclear pore complex dynamics for rapid cell division
Related Articles
The DEAD-box helicase eIF4A1/2 acts as RNA chaperone during mitotic exit enabling chromatin decondensation
During mitosis, chromosomes condense and decondense to segregate faithfully and undamaged. The exact molecular mechanisms are not well understood. We identify the DEAD-box helicase eIF4A1/2 as a critical factor in this process. In a cell-free condensation assay eIF4A1/2 is crucial for this process, relying on its RNA-binding ability but not its ATPase activity. Reducing eIF4A1/2 levels in cells consistently slows down chromatin decondensation during nuclear reformation. Conversely, increasing eIF4A1/2 concentration on mitotic chromosomes accelerates their decondensation. The absence of eIF4A1/2 affects the perichromatin layer, which surrounds the chromosomes during mitosis and consists of RNA and mainly nucleolar proteins. In vitro, eIF4A1/2 acts as an RNA chaperone, dissociating biomolecular condensates of RNA and perichromatin proteins. During mitosis, the chaperone activity of eIF4A1/2 is required to regulate the composition and fluidity of the perichromatin layer, which is crucial for the dynamic reorganization of chromatin as cells exit mitosis.
CeDaD—a novel assay for simultaneous tracking of cell death and division in a single population
The cell division cycle and the various forms of programmed cell death are interconnected. A prominent example is the tumor suppressor p53, which not only induces apoptosis but also plays an important role in the arrest of the cell cycle. Consequently, simultaneous analysis of cell division and cell death is frequently of significant interest in cell biology research. Traditionally, these processes require distinct assays, making concurrent analysis challenging. To address this, we present a novel combined assay, called CeDaD assay—Cell Death and Division assay—which allows for the simultaneous quantification of cell division and cell death within a single-cell population. This assay utilizes a straightforward flow cytometric approach, combining a staining based on carboxyfluorescein succinimidyl ester (CFSE) to monitor cell division with an annexin V-derived staining to assess the extent of cell death.
Personalized bioceramic grafts for craniomaxillofacial bone regeneration
The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.
Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3
Gasdermin D and gasdermin A3 belong to the same family of pore-forming proteins and executors of pyroptosis, a form of programmed cell death. To unveil the process of their pore formation, we examine the energy landscapes upon insertion of the gasdermin D and A3 monomers into a lipid bilayer by extensive atomistic molecular dynamics simulations. We reveal a lower free energy barrier of membrane insertion for gasdermin D than for gasdermin A3 and a preference of gasdermin D for the membrane-inserted and of gasdermin A3 for the membrane-adsorbed state, suggesting that gasdermin D first inserts and then oligomerizes while gasdermin A3 oligomerizes and then inserts. Gasdermin D stabilizes itself in the membrane by forming more salt bridges and pulling phosphatidylethanolamine lipids and more water into the membrane. Gasdermin-lipid interactions support the pore formation. Our findings suggest that both the gasdermin species and the lipid composition modulate gasdermin pore formation.
Cytoplasmic flow is a cell size sensor that scales anaphase
During early embryogenesis, fast mitotic cycles without interphase lead to a decrease in cell size, while scaling mechanisms must keep cellular structures proportional to cell size. For instance, as cells become smaller, if the position of nuclear envelope reformation (NER) did not adapt, NER would have to occur beyond the cell boundary. Here we found that NER position in anaphase scales with cell size via changes in chromosome motility, mediated by cytoplasmic flows that themselves scale with cell size. Flows are a consequence of friction between viscous cytoplasm and bulky cargo transported by dynein on astral microtubules. As an emerging property, confinement in cells of different sizes yields scaling of cytoplasmic flows. Thus, flows behave like a cell geometry sensor: astral microtubules approach the boundary causing flow velocity changes, which then affect the velocity of chromosome separation, thus scaling NER.
Responses