Publications by authors named "Charlotte Kelley"

Article Synopsis
  • Focal adhesions are assemblies formed around activated integrin receptors, and the study investigates how these structures maintain their flexible, liquid-like properties in the cell.
  • Researchers reconstitute focal adhesion components, observing that proteins like talin and vinculin undergo liquid-liquid phase separation, particularly when interacting with specific membrane lipids.
  • The findings suggest that lipid binding activates these proteins, leading to their clustering on membranes, which helps early focal adhesions stay organized yet dynamic, allowing for quick assembly and disassembly.
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  • Metastasis is the leading cause of death in breast cancer, necessitating an understanding of tumor cell migration and its correlation between in vitro and in vivo behavior.
  • In a study using immunocompromised mice, six human triple-negative breast cancer (TNBC) cell lines were evaluated for their tumor growth, metastasis, and characteristics such as morphology, proliferation, and motility.
  • The findings categorized cell lines by their metastatic potential and showed that morphological metrics were the best predictors of tumor growth and metastasis, while in vitro motility assays did not significantly correlate with in vivo outcomes.
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  • Metastasis is a major cause of death in breast cancer, involving processes like local invasion and colonization of distant organs, which are poorly understood across different human breast cancer cell lines.
  • This study classified six triple-negative breast cancer cell lines in a mouse model based on their tumor growth and metastasis characteristics, revealing varying levels of tumorigenicity and metastatic potential.
  • The researchers found that cell morphology metrics were the best predictors of metastasis, while no single motility assay consistently correlated with metastatic potential.
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  • The study focuses on how actin assembly, necessary for processes like endocytosis at synaptic membranes, is tightly controlled by specific proteins to ensure effective membrane remodeling.
  • It explains that the endocytic proteins Nwk/FCHSD2, Dap160/intersectin, and WASp interact in a way that both relieves autoinhibition and encourages targeted actin assembly during synaptic activity.
  • Ultimately, the research highlights that these protein interactions not only prevent unwanted actin structures but also enhance synaptic endocytosis, indicating a dual role in regulating actin assembly in neurons.
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  • The development of minimal cell division machineries in synthetic biology focuses on controlling large structures like Giant Unilamellar Vesicles (GUVs) using active elements much larger than molecular structures.
  • The study employs advanced methods to encapsulate and analyze bundled actin filaments in GUVs, revealing key parameters that allow actin polymerization to mimic various cellular networks.
  • Findings indicate that effective membrane binding is essential for forming stable actin rings, which contract and deform the vesicles when activated by myosin motors, while cortex-like actin networks can stabilize these deformations.
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  • Actomyosin networks are crucial for coordinated cell contractions, and the C. elegans spermatheca serves as a model to study their organization.
  • The protein FLN-1/filamin is essential for creating a stable arrangement of actomyosin fibers; without it, fibers detach and aggregate inappropriately.
  • The absence of filamin disrupts not only actin and myosin distribution but also affects nuclear positioning and organelle organization, highlighting its role in cellular structure maintenance.
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  • - The study investigates the link between endoplasmic reticulum (ER) and mitochondria dysfunctions and their roles in aging, showing that controlling their communication may promote longevity.
  • - In the roundworm Caenorhabditis elegans, reducing the function of the atf-6 protein increases lifespan by balancing calcium levels and signaling between the ER and mitochondria.
  • - Proper ER calcium release and mitochondrial calcium import are crucial for longevity, with disruptions in these processes leading to impaired energy production and shorter lifespans in atf-6 mutants.
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Focal adhesions (FA) are large macromolecular assemblies which help transmit mechanical forces and regulatory signals between the extracellular matrix and an interacting cell. Two key proteins talin and vinculin connecting integrin to actomyosin networks in the cell. Both proteins bind to F-actin and each other, providing a foundation for network formation within FAs.

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Actomyosin-based contractility in smooth muscle and nonmuscle cells is regulated by signaling through the small GTPase Rho and by calcium-activated pathways. We use the myoepithelial cells of the spermatheca to study the mechanisms of coordinated myosin activation in vivo. Here, we show that redox signaling modulates RHO-1/Rho activity in this contractile tissue.

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Article Synopsis
  • Focal adhesions (FAs) are important for cell functions like adhesion and movement, with talin being a key protein that links integrins to the cytoskeleton.
  • Researchers used cryoelectron microscopy to explore the structure of talin1, finding it has a self-inhibiting mechanism that prevents integrin activation when needed.
  • The study shows that talin can switch between a compact form and a longer, active conformation, which is essential for regulating cell adhesion and signaling processes.
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Article Synopsis
  • * Key cell types include gonadal sheath cells, spermathecal cells, and a spermatheca-uterine valve, all of which contract in a coordinated way.
  • * Research on this system has advanced understanding of how acto-myosin networks are formed and regulated during contractions in living organisms.
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Interactions between the distal tip cell and germline stem cells maintain a proliferative pool of mitotic cells in the Caenorhabditis elegans gonad. A new study shows that escaped germline stem cells induce nearby muscle cells to reach out and wrap around them, forming an ectopic niche similar to the native gonadal germ cell niche.

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  • The cilium is an important cellular structure involved in movement and signaling, and intraflagellar transport (IFT) helps deliver essential materials to it.
  • IFT172, a key component for cilium formation, is challenging to study due to its large size and structure, which includes two globular domains connected by a long rod-like section.
  • Research shows that IFT172 can interact with membranes to create smaller vesicles and can adopt two different shapes, influenced by lipids and detergents, indicating it may have multiple roles within the IFT process.
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We identify the Caenorhabditis elegans myosin light-chain kinase, MLCK-1, required for contraction of spermathecae. During contraction, MLCK-1 moves from the apical cell boundaries to the basal actomyosin bundles, where it stabilizes myosin downstream of calcium signaling. MLCK and ROCK act in distinct subsets of cells to coordinate the timing of contraction.

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  • Autoinhibitory interactions between the SH3 and F-BAR domains of F-BAR proteins regulate membrane remodeling, but the structural basis of this autoregulation and its effect on cellular interactions are not well understood.
  • The study utilized single-particle electron microscopy to analyze the F-BAR protein Nervous Wreck (Nwk) in soluble and membrane-bound forms, revealing that the SH3 domains reposition rather than fully detach upon membrane binding.
  • Findings indicate that Nwk's autoregulation limits the activity of SH3 domains in actin filament assembly and affects synaptic growth and organization in Drosophila neurons, suggesting a coordinated relationship between membrane interactions and SH3 domain functions.
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Article Synopsis
  • F-BAR domain proteins are crucial for sensing and shaping membrane curvature by interacting with specific negatively charged lipids but how these interactions are controlled is not well understood.
  • * In this study, researchers found that the Drosophila Nervous Wreck (Nwk) protein uses a C-terminal SH3 domain to autoregulate its own F-BAR domain, impacting how it interacts with membranes.
  • * Autoregulation does not simply act as a switch; instead, it enhances Nwk's ability to form higher-order structures and affects membrane deformation, depending on the negative charge of the membrane composition.*
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F-BAR domains form crescent-shaped dimers that bind to and deform lipid bilayers, and play a role in many cellular processes requiring membrane remodeling, including endocytosis and cell morphogenesis. Nervous Wreck (NWK) encodes an F-BAR/SH3 protein that regulates synapse growth in Drosophila. Unlike conventional F-BAR proteins that assemble tip-to-tip into filaments and helical arrays around membrane tubules, the Nwk F-BAR domain instead assembles into zigzags, creating ridges and periodic scallops on membranes in vitro.

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Article Synopsis
  • Eukaryotic cells rely on F-BAR domain proteins, which are capable of bending membranes for shaping cellular compartments, but their varying membrane-deforming activities are not fully understood.
  • The Nwk protein's F-BAR domain forms a unique zigzag structure that enhances its ability to create distinct membrane shapes, differing from other F-BAR proteins.
  • This study reveals how structural features of the Nwk F-BAR domain contribute to its membrane sculpting abilities, highlighting a new aspect of how F-BAR proteins can induce various membrane curvatures.
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Vaginal atrophy has a host of symptoms that affect the vaginal health of post-menopausal women. Evaluating and determining the efficacy of treatment with estrogen requires careful consideration. An overview of the hormonal changes during menopause, its effect on vaginal health, and recommendations for evaluation and treatment of vaginal atrophy are provided.

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