[Molecular biology of neurosecretion and its inhibition bu tetanus and botulinum toxins (review)].
Signal transfer between neurons and between neurons and muscle cells is mediated by the secretion of neurotransmitters. The axon of the presynaptic cell contains synaptic vesicles, the storage organelles for neurotransmitters. Arrival of an action potential causes calcium-influx into the axon and leads to fusion of synaptic vesicles with the presynaptic plasma membrane. Recently, the events between calcium-influx and membrane fusion were elucidated on a molecular level. The family of SNARE-proteins was identified as the key players in neurosecretion. They are located on synaptic vesicles (VAMP) or on the presynaptic plasma membrane (syntaxin, SNAP-25). Intimate protein-protein interactions between the SNARE-proteins are responsible for the attachment and merger of vesicle and the plasma membrane. Fusion is triggered by calcium-binding to synaptotagmin, another protein recently identified on synaptic vesicles. The molecular mechanism of the action of clostridial neurotoxins was also elucidated. Botulinum-as well as Tetanus toxins are proteases which cleave neuronal SNARE-proteins. This explains the long known inhibition of neurosecretion caused by these toxins. The proteolytic action of Tetanus- and Botulinum toxin occurs in different types of neurons, resulting in a stimulatory or inhibitory effect on muscle cells. This selective degradation of SNAREs explains the opposing clinical signs of tetanus (cramps) and botulismus (paralysis).
Institut für Immunologie und Molekularbiologie, Fachbereich Veterinärmedizin der Freien Universität Berlin.
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D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008967:Molecular Biology; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D050600:SNARE Proteins; D013572:Synaptic Vesicles / Q000187:drug effects / Q000502:physiology*; D013744:Tetanus Toxin / Q000494:pharmacology*; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D050600:SNARE Proteins; D013744:Tetanus Toxin; D033921:Vesicular Transport Proteins; D001905:Botulinum Toxins
Molekularbiologie der Neurosekretion und ihre Hemmung durch Tetanus- und Botulinum-Toxin (Ubersichtsreferat).