32 research outputs found

    Colocalization of Protein Kinase A with Adenylyl Cyclase Enhances Protein Kinase A Activity during Induction of Long-Lasting Long-Term-Potentiation

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    The ability of neurons to differentially respond to specific temporal and spatial input patterns underlies information storage in neural circuits. One means of achieving spatial specificity is to restrict signaling molecules to particular subcellular compartments using anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Disruption of protein kinase A (PKA) anchoring to AKAPs impairs a PKA-dependent form of long term potentiation (LTP) in the hippocampus. To investigate the role of localized PKA signaling in LTP, we developed a stochastic reaction-diffusion model of the signaling pathways leading to PKA activation in CA1 pyramidal neurons. Simulations investigated whether the role of anchoring is to locate kinases near molecules that activate them, or near their target molecules. The results show that anchoring PKA with adenylyl cyclase (which produces cAMP that activates PKA) produces significantly greater PKA activity, and phosphorylation of both inhibitor-1 and AMPA receptor GluR1 subunit on S845, than when PKA is anchored apart from adenylyl cyclase. The spatial microdomain of cAMP was smaller than that of PKA suggesting that anchoring PKA near its source of cAMP is critical because inactivation by phosphodiesterase limits diffusion of cAMP. The prediction that the role of anchoring is to colocalize PKA near adenylyl cyclase was confirmed by experimentally rescuing the deficit in LTP produced by disruption of PKA anchoring using phosphodiesterase inhibitors. Additional experiments confirm the model prediction that disruption of anchoring impairs S845 phosphorylation produced by forskolin-induced synaptic potentiation. Collectively, these results show that locating PKA near adenylyl cyclase is a critical function of anchoring

    Synaptic AMPA receptor composition in development, plasticity and disease

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    Synaptic AMPA receptor composition in development, plasticity and disease

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    Silica deposits in the Nili Patera caldera on the Syrtis Major volcanic complex on Mars

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    The martian surface features abundant volcanoes and evidence for past liquid water. Extant or relict martian volcanic hydrothermal systems have therefore been sought in the pursuit of evidence for habitable environments. The Mars Exploration Rover, Spirit, detected deposits highly enriched in silica with accessory minerals, suggesting formation by hydrothermal leaching of basaltic rocks by low-pH solutions. However, extensive erosion has obscured the context of the formation environment of these deposits. Silica deposits have also been identified remotely, but also with limited contextual clues to their formation; aqueous alteration products of basalt and volcanic ash are the most likely sources. Here we report the detection from orbit of hydrated silica deposits on the flanks of a volcanic cone in the martian Syrtis Major caldera complex. Near-infrared observations show dozens of localized hydrated silica deposits. As a result of the morphology of these deposits and their location in and around the cone summit, we suggest that the deposits were produced by a volcanically driven hydrothermal system. The cone and associated lava flows post-date Early Hesperian volcano formation. We conclude that, if a relict hydrothermal system was associated with the silica deposits, it may preserve one of the most recent habitable microenvironments on Mars

    Deep crustal carbonate rocks exposed by meteor impact on Mars

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    The surface of Mars is cold, dry, oxidizing, acidic and inhospitable to life. Similar conditions may have persisted for billions of years, suggesting that the best place to search for habitable environments is the subsurface. One hint of habitable conditions at depth is the presence of atmospheric methane, which may have formed through hydrothermal processes in the crust in the presence of CO2. The observation of hydrated minerals excavated by some impact craters suggests that ancient hydrothermal systems may have existed in the subsurface, but until now, none of those deposits has been linked to carbonate minerals and CO2 -rich environments. Previous detections of carbonate minerals that could be linked to an ancient CO2 -rich surface environment have been sparse. Here we show spectral evidence for carbonate- and phyllosilicate-bearing, layered and foliated bedrock exhumed from deep (about 6km) within the martian crust by a meteor impact. The mineral assemblage, textural properties and geologic context of the deposits indicate that these rocks are probably ancient sediments that were metamorphosed during burial by younger volcanic materials from the nearby Syrtis Major volcano. We suggest that these buried layered carbonates might be only a small part of a much more extensive ancient carbonate sedimentary record that has been buried by volcanic resurfacing and impact ejecta. Our discovery may help explain the origin of other carbonates on Mars and indicates a high-priority site for future exobiological exploration. © 2010 Macmillan Publishers Limited. All rights reserved. © 2010 Macmillan Publishers Limited. All rights reserved.Link_to_subscribed_fulltex
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