Journal Article10.1152/PHYSREV.2000.80.2.717
Neurotoxins Affecting Neuroexocytosis
TL;DR: The mechanism of action of three groups of presynaptic neurotoxins that interfere directly with the process of neurotransmitter release is reviewed, whereas presynapses acting on ion channels are not dealt with here.
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Abstract: Nerve terminals are specific sites of action of a very large number of toxins produced by many different organisms. The mechanism of action of three groups of presynaptic neurotoxins that interfere directly with the process of neurotransmitter release is reviewed, whereas presynaptic neurotoxins acting on ion channels are not dealt with here. These neurotoxins can be grouped in three large families: 1) the clostridial neurotoxins that act inside nerves and block neurotransmitter release via their metalloproteolytic activity directed specifically on SNARE proteins; 2) the snake presynaptic neurotoxins with phospholipase A(2) activity, whose site of action is still undefined and which induce the release of acethylcholine followed by impairment of synaptic functions; and 3) the excitatory latrotoxin-like neurotoxins that induce a massive release of neurotransmitter at peripheral and central synapses. Their modes of binding, sites of action, and biochemical activities are discussed in relation to the symptoms of the diseases they cause. The use of these toxins in cell biology and neuroscience is considered as well as the therapeutic utilization of the botulinum neurotoxins in human diseases characterized by hyperfunction of cholinergic terminals.
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Citations
Multiple roles of calcium ions in the regulation of neurotransmitter release.
Erwin Neher,Takeshi Sakaba +1 more
TL;DR: Two distinct roles of [Ca(2+)] are proposed in vesicle recruitment: one accelerating "molecular priming" (vesicle docking and the buildup of a release machinery), the other promoting the tight coupling between releasable vesicles and Ca(2+) channels.
948
Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement
Clifford P. Brangwynne,Fred C. MacKintosh,Sanjay Kumar,Nicholas A. Geisse,Jennifer Talbot,Lakshminarayanan Mahadevan,Kevin Kit Parker,Donald E. Ingber,David A. Weitz +8 more
TL;DR: It is shown that intracellular microtubules do bear large-scale compressive loads from a variety of physiological forces, but their buckling wavelength is reduced significantly because of mechanical coupling to the surrounding elastic cytoskeleton, suggesting they can make a more significant structural contribution to the mechanical behavior of the cell than previously thought possible.
Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis.
Philip Washbourne,Peter M. Thompson M.D.,Peter M. Thompson M.D.,Mario Carta,Edmar Tavares da Costa,Edmar Tavares da Costa,James R. Mathews,Guillermina López-Bendito,Zoltán Molnár,Mark W. Becher,C. Fernando Valenzuela,L. Donald Partridge,Michael Wilson +12 more
TL;DR: This work shows that the neural t-SNARE (target-membrane-associated–soluble N-ethylmaleimide fusion protein attachment protein (SNAP) receptor SNAP-25 is not required for nerve growth or stimulus-independent neurotransmitter release, but is essential for evoked synaptic transmission at neuromuscular junctions and central synapses.
569
Botulinum neurotoxins: genetic, structural and mechanistic insights
TL;DR: This Review discusses recent studies that have improved the understanding of the genetics and structure of the BoNT complexes and describes recent insights into the mechanisms of BoNT entry into the general circulation, neuronal binding, membrane translocation and neuroparalysis.
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Identification of the Major Steps in Botulinum Toxin Action
TL;DR: This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission, as well as an agent that can be used to treat disease.
557
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TL;DR: It is shown that nitric oxide donors and ONOO are each able to trigger apoptosis of mouse cerebellar granule cells by an excitotoxic mechanism requiring exocytosis and NMDA receptor‐mediated intracellular Ca2+ overload.
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TL;DR: In this paper, the poison glands of the spider Latrodectus tredecuttatus were found to have approximately the same toxicity, on a body weight basis, toward the housefly and the guinea pig (10−12 LD 50 per milligram of protein per kilogram of animal).
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