100 research outputs found

    Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots

    Get PDF
    G-protein-coupled receptors mediate the biological effects of many hormones and neurotransmitters and are important pharmacological targets. They transmit their signals to the cell interior by interacting with G proteins. However, it is unclear how receptors and G proteins meet, interact and couple. Here we analyse the concerted motion of G-protein-coupled receptors and G proteins on the plasma membrane and provide a quantitative model that reveals the key factors that underlie the high spatiotemporal complexity of their interactions. Using two-colour, single-molecule imaging we visualize interactions between individual receptors and G proteins at the surface of living cells. Under basal conditions, receptors and G proteins form activity-dependent complexes that last for around one second. Agonists specifically regulate the kinetics of receptor-G protein interactions, mainly by increasing their association rate. We find hot spots on the plasma membrane, at least partially defined by the cytoskeleton and clathrin-coated pits, in which receptors and G proteins are confined and preferentially couple. Imaging with the nanobody Nb37 suggests that signalling by G-protein-coupled receptors occurs preferentially at these hot spots. These findings shed new light on the dynamic interactions that control G-protein-coupled receptor signalling

    Impacts of Warming and Acidification on Coral Calcification Linked to Photosymbiont Loss and Deregulation of Calcifying Fluid pH

    Get PDF
    Corals are globally important calcifiers that exhibit complex responses to anthropogenic warming and acidification. Although coral calcification is supported by high seawater pH, photosynthesis by the algal symbionts of zooxanthellate corals can be promoted by elevated pCO2. To investigate the mechanisms underlying corals’ complex responses to global change, three species of tropical zooxanthellate corals (Stylophora pistillata, Pocillopora damicornis, and Seriatopora hystrix) and one species of asymbiotic cold-water coral (Desmophyllum pertusum, syn. Lophelia pertusa) were cultured under a range of ocean acidification and warming scenarios. Under control temperatures, all tropical species exhibited increased calcification rates in response to increasing pCO2. However, the tropical species’ response to increasing pCO2 flattened when they lost symbionts (i.e., bleached) under the high-temperature treatments—suggesting that the loss of symbionts neutralized the benefit of increased pCO2 on calcification rate. Notably, the cold-water species that lacks symbionts exhibited a negative calcification response to increasing pCO2, although this negative response was partially ameliorated under elevated temperature. All four species elevated their calcifying fluid pH relative to seawater pH under all pCO2 treatments, and the magnitude of this offset (Δ[H+]) increased with increasing pCO2. Furthermore, calcifying fluid pH decreased along with symbiont abundance under thermal stress for the one species in which calcifying fluid pH was measured under both temperature treatments. This observation suggests a mechanistic link between photosymbiont loss (‘bleaching’) and impairment of zooxanthellate corals’ ability to elevate calcifying fluid pH in support of calcification under heat stress. This study supports the assertion that thermally induced loss of photosymbionts impairs tropical zooxanthellate corals’ ability to cope with CO2-induced ocean acidification

    Student attitudes toward experiential education

    No full text
    There is no abstract available for this research paper.Thesis (M.A.)Department of Secondary, Higher, and Foundations of Educatio

    Bayesian inference and asset pricing

    No full text
    SIGLEAvailable from British Library Document Supply Centre- DSC:6392.9259(QMWC-DE-DP--314) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    The costs of commodity price uncertainty and instability

    No full text
    Revised editionSIGLEAvailable from British Library Document Supply Centre- DSC:6392.9259(QMWC-DE-P--266) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Consumption and asset pricing What do UK data tell us?

    No full text
    Available from British Library Document Supply Centre- DSC:6392.9259(QMWC-DE-P--346) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
    • …
    corecore