title: Synaptic vesicle proteins: targets and routes for botulinum neurotoxins.
abstract: Synaptic vesicles (SV) are key organelles of neuronal communication. SV are responsible for the storage of neurotransmitters, which are released by Ca(2+)-dependent exocytosis. After release and interaction with postsynaptic receptors, transmitters rapidly diffuse out of the synaptic cleft and are sequestered by plasma membrane transporters (in some cases following enzymatic conversion). SVs undergo endocytosis and are refilled by specific vesicular transmitter transporters different in the various neuronal subtypes. Besides these differences, SVs in general are equipped with a remarkable common set of proteins. Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release from almost all types of neurons by cleaving proteins required for membrane fusion localized either to SVs (synaptobrevin) or to the plasma membrane (SNAP-25 and syntaxin) depending on the BoNT serotype. To enter the neuronal cytoplasm, BoNTs specifically interact with the luminal domain of SV proteins (synaptotagmin or SV2, depending on serotype) transiently exposed during exocytotic membrane fusion and occurring in almost every neuron. Thus, the highly specific interaction with luminal domains of SV proteins commonly expressed on all SV types is one reason why BoNTs exhibit such a high neuronal specificity but attack almost every neuron type.
authors.affiliation: AG Functional Cell Biology, Institute for Integrative Neuroanatomy, Charité-Universitätsmedizin, Philippstr 12, 10115 Berlin, Germany. gudrun.ahnert@charite.de
authors.forename: Gudrun
authors.initials: G
authors.lastname: Ahnert-Hilger
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Münster-Wandowski
authors.forename: Markus
authors.initials: M
authors.lastname: Höltje
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism* / Q000633:toxicity; D001906:Botulism / Q000382:microbiology / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D003014:Clostridium botulinum / Q000472:pathogenicity; D005089:Exocytosis; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000382:microbiology; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D021381:Protein Transport; D059748:Proteolysis; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050857:Synaptotagmins / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; C494209:Snap25 protein, mouse; C489614:Sv2a protein, mouse; D050825:Synaptosomal-Associated Protein 25; D050857:Synaptotagmins; D001905:Botulinum Toxins