Browsing by Subject "Membrane Microdomains"

Now showing 1 - 3 of 3
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    Glutamate receptor dynamics in dendritic microdomains.
    (Neuron, 2008-05) Newpher, Thomas M; Ehlers, Michael D
    Among diverse factors regulating excitatory synaptic transmission, the abundance of postsynaptic glutamate receptors figures prominently in molecular memory and learning-related synaptic plasticity. To allow for both long-term maintenance of synaptic transmission and acute changes in synaptic strength, the relative rates of glutamate receptor insertion and removal must be tightly regulated. Interactions with scaffolding proteins control the targeting and signaling properties of glutamate receptors within the postsynaptic membrane. In addition, extrasynaptic receptor populations control the equilibrium of receptor exchange at synapses and activate distinct signaling pathways involved in plasticity. Here, we review recent findings that have shaped our current understanding of receptor mobility between synaptic and extrasynaptic compartments at glutamatergic synapses, focusing on AMPA and NMDA receptors. We also examine the cooperative relationship between intracellular trafficking and surface diffusion of glutamate receptors that underlies the expression of learning-related synaptic plasticity.
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    Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation.
    (2010) Jin, Cong
    In recent years, the incidence of allergic asthma as well as the severity of disease has rapidly increased worldwide. Numerous epidemiological studies have related the exacerbation of allergic asthma with exposure to increased ambient particles from air pollutants. However, the mechanism by which particulate allergens (pAg) exacerbate allergic asthma remains undefined. To evaluate this, we modeled environmental pAg induced allergic asthma by exposing mice to polystyrene beads coated with natural allergen extracts. Compared to equal amounts of soluble allergen extracts (sAg), pAg triggered markedly enhanced airway hyper-responsiveness and pulmonary eosinophilia in allergen sensitized mice. The cellular basis for this effect was determined to be mast cells (MCs), as both airway allergic responses were attenuated in MC deficient KitWsh/KitW-sh mice compared to MC reconstituted KitW-sh/KitW-sh mice. The divergent responses of MCs to pAg versus sAg were due to differences in the termination rate of IgE/FcεRI initiated signaling. Following ligation of sAg, IgE/FcεRI rapidly shuttled into a degradative endosome/lysosome pathway. However, following ligation by pAg, IgE/FcεRI migrated into lipid raft enriched compartments and subsequently failed to follow a degradative pathway, which resulted in a prolonged signaling and heightened synthesis of proinflammatory mediators. These observations highlight the overlooked contributions of the particulate nature of allergens and mast cell endocytic circuitry to the aggravation of allergic asthma.
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    Spine microdomains for postsynaptic signaling and plasticity.
    (Trends in cell biology, 2009-05) Newpher, Thomas M; Ehlers, Michael D
    Changes in the molecular composition and signaling properties of excitatory glutamatergic synapses onto dendritic spines mediate learning-related plasticity in the mammalian brain. This molecular adaptation serves as the most celebrated cell biological model for learning and memory. Within their micron-sized dimensions, dendritic spines restrict the diffusion of signaling molecules and spatially confine the activation of signal transduction pathways. Much of this local regulation occurs by spatial compartmentalization of glutamate receptors. Here, we review recently identified cell biological mechanisms regulating glutamate receptor mobility within individual dendritic spines. We discuss the emerging functions of glutamate receptors residing within sub-spine microdomains and propose a model for distinct signaling platforms with specialized functions in synaptic plasticity.