The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Thomas C Sudhof - One of the best experts on this subject based on the ideXlab platform.
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α-Latrotoxin and Its Receptors: Neurexins and CIRL/Latrophilins
Annual review of neuroscience, 2001Co-Authors: Thomas C SudhofAbstract:▪ Abstract α-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. α-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, α-latrotoxin binds to two distinct families of neuronal cell-surface Receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion. Binding of α-latrotoxin to these Receptors does not in itself trigger exocytosis but serves to recruit the toxin to the Synapse. Receptor-bound α-latrotoxin then inserts into the presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter-specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA, acetylcholine) is induced in a calcium-independent manner by a direct intracellular action of α-latrotoxin, while exocytosis of catecholamines requires extracellular calcium. Elucidation of precisely how α-latrotoxin works is likely ...
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α latrotoxin and its Receptors neurexins and cirl latrophilins
Annual Review of Neuroscience, 2001Co-Authors: Thomas C SudhofAbstract:▪ Abstract α-Latrotoxin, a potent neurotoxin from black widow spider venom, triggers synaptic vesicle exocytosis from presynaptic nerve terminals. α-Latrotoxin is a large protein toxin (120 kDa) that contains 22 ankyrin repeats. In stimulating exocytosis, α-latrotoxin binds to two distinct families of neuronal cell-surface Receptors, neurexins and CLs (Cirl/latrophilins), which probably have a physiological function in synaptic cell adhesion. Binding of α-latrotoxin to these Receptors does not in itself trigger exocytosis but serves to recruit the toxin to the Synapse. Receptor-bound α-latrotoxin then inserts into the presynaptic plasma membrane to stimulate exocytosis by two distinct transmitter-specific mechanisms. Exocytosis of classical neurotransmitters (glutamate, GABA, acetylcholine) is induced in a calcium-independent manner by a direct intracellular action of α-latrotoxin, while exocytosis of catecholamines requires extracellular calcium. Elucidation of precisely how α-latrotoxin works is likely ...
Mark J West - One of the best experts on this subject based on the ideXlab platform.
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Age-Related Neuronal Loss in the Cerebral Cortex
Cerebral Cortex, 1999Co-Authors: Mark J WestAbstract:Age-related neuronal loss in the cerebral cortex has been the subject of numerous studies aimed at identifying the structural basis of senescent decline in neural function. Because cortical neurons are not generated or replaced during adult life, an evaluation of neuronal loss represents a simple means for quantifying the cumulative effects of the neurodegenerative aging process. As a single parameter, neuron number represents one fundamental expression of the information processing capacity of the tissue, that is, the number of integrative entities with separate output channels. It also provides a quantitative, structural framework in which changes in other parameters, such a Synapse, Receptor, and dendrite number, can more rigorously be evaluated.
Cory Berkland - One of the best experts on this subject based on the ideXlab platform.
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Autoimmune therapies targeting costimulation and emerging trends in multivalent therapeutics.
Therapeutic delivery, 2011Co-Authors: Chuda Chittasupho, Teruna J. Siahaan, Charlotte M. Vines, Cory BerklandAbstract:Proteins participating in immunological signaling have emerged as important targets for controlling the immune response. A multitude of Receptor–ligand pairs that regulate signaling pathways of the immune response have been identified. In the complex milieu of immune signaling, therapeutic agents targeting mediators of cellular signaling often either activate an inflammatory immune response or induce tolerance. This review is primarily focused on therapeutics that inhibit the inflammatory immune response by targeting membrane-bound proteins regulating costimulation or mediating immune-cell adhesion. Many of these signals participate in larger, organized structures such as the immunological Synapse. Receptor clustering and arrangement into organized structures is also reviewed and emerging trends implicating a potential role for multivalent therapeutics is posited.
Steven H Devries - One of the best experts on this subject based on the ideXlab platform.
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mechanism of high frequency signaling at a depressing ribbon Synapse
Neuron, 2016Co-Authors: Chad P Grabner, Charles P Ratliff, Adam C Light, Steven H DevriesAbstract:Ribbon Synapses mediate continuous release in neurons that have graded voltage responses. While mammalian retinas can signal visual flicker at 80-100 Hz, the time constant, τ, for the refilling of a depleted vesicle release pool at cone photoReceptor ribbons is 0.7-1.1 s. Due to this prolonged depression, the mechanism for encoding high temporal frequencies is unclear. To determine the mechanism of high-frequency signaling, we focused on an "Off" cone bipolar cell type in the ground squirrel, the cb2, whose transient postsynaptic responses recovered following presynaptic depletion with a τ of ∼0.1 s, or 7- to 10-fold faster than the τ for presynaptic pool refilling. The difference in recovery time course is caused by AMPA Receptor saturation, where partial refilling of the presynaptic pool is sufficient for a full postsynaptic response. By limiting the dynamic range of the Synapse, Receptor saturation counteracts ribbon depression to produce rapid recovery and facilitate high-frequency signaling.
Shoshana Levy - One of the best experts on this subject based on the ideXlab platform.
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CD81 as a tumor target
Biochemical Society transactions, 2017Co-Authors: Felipe Vences-catalán, Caroline Duault, Chiung-chi Kuo, Ranjani Rajapaksa, Ronald Levy, Shoshana LevyAbstract:CD81 participates in a variety of important cellular processes such as membrane organization, protein trafficking, cellular fusion and cell-cell interactions. In the immune system, CD81 regulates immune Synapse, Receptor clustering and signaling; it also mediates adaptive and innate immune suppression. CD81 is a gateway in hepatocytes for pathogens such as hepatitis C virus and Plasmodium; it also confers susceptibility to Listeria infection. These diverse biological roles are due to the tendency of CD81 to associate with other tetraspanins and with cell-specific partner proteins, which provide the cells with a signaling platform. CD81 has also been shown to regulate cell migration and invasion, and has therefore been implicated in cancer progression. Indeed, we have recently shown that CD81 contributes to tumor growth and metastasis. CD81 is expressed in most types of cancer, including breast, lung, prostate, melanoma, brain cancer and lymphoma, and the overexpression or down-regulation of this molecule has been correlated with either good or bad prognosis. Here, we discuss the role of CD81 in cancer and its potential therapeutic use as a tumor target.
