Synaptic vesicle exocytosis

Heuser, J. E. Synaptic vesicle exocytosis revealed in quick-frozen frog NMJ treated with 4-aminopyridine and given a single electric shock. In W. M. Cowan and J. Ferrendelli (eds.), Approaches to the Cell Biology of Neurons. Bethesda, MD Society for Neuroscience, 1976, pp. 215-239. 

Detection of Synaptic Vesicle Exocytosis and Endocytosis Using... 

The experiments using these optical tools consistently supported the premise that synaptic vesicle exocytosis and endocytosis are tightly coupled processes. This largely kinetic coupling is also backed up by recent molecular evidence that proteins critical for exocytosis such as synaptotagmin and synaptobrevin, are also essential for triggering endocytosis (Poskanzer et al., 2003 Deak et al., 2004 Nicholson-Tomishima and Ryan, 2004). 

Fig. 4 Stages in synaptic vesicle exocytosis. Putative intermediate steps on the molecular pathway to synaptic vesicle fusion. Vesicle delivery and tethering to the presynaptic membrane most likely involves Rab-proteins and their effectors. So far, the nature of a speculative docking complex (dc) is unclear, but docking appears to be independent from SNARE proteins. In the primed state, SNAREs have assembled into a complex probably stabilized by complexin (Cpx). The fusion reaction is arrested until the intracellular calcium concentration increases. The putative calcium sensor for fast neurotransmitter release, synaptotagmin 1 (Syt), binds to intracellular calcium and in turn triggers fusion by associating with the presynaptic membrane and interacting with the SNARE complex, thereby displacing complexin (Tang et al. 2006).

Tang J, Maximov A, Shin OH, Dai H, Rizo J, Sudhof TC (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126 1175-87 Toonen RF, Verhage M (2003) Vesicle trafficking pleasure and pain from SM genes. Trends Cell Biol. 13 177-86... 

Bleck (1989) Clinical aspects of tetanus. In Simpson LL (ed) Botulinum neurotoxin and tetanus toxin. Academic Press, San Diego, CA, pp 379-98 Bonanomi D, Pennuto M, Rigoni M, Rossetto O, Montecucco C et al. (2005) Taipoxin induces synaptic vesicle exocytosis and disrupts the interaction of synaptophysin I with VAMP2. Mol Pharmacol 67 1901-8... 

Okamoto M, Siidhof TC (1997) Mints, Muncl8-interacting proteins in synaptic vesicle exocytosis. JBiolChem 272 31459-64... 

Balaji, J., and Ryan, T. A. (2007). Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis are coupled by a single stochastic mode. Proc. Natl. Acad. Sci USA 104, 20576—20581. 

Butz S, Okamoto M, Sudhof TC. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 1998 94 773-782. 

Valtorta F, Pennuto M, Bonanomi D, Benfenati F. 2004. Synaptophysin Leading actor or walk-on role in synaptic vesicle exocytosis Bioessays 26 445-453. 

Binds to synaptic vesicle protein SV2A, which is involved in synaptic vesicle exocytosis... 

Willig KI, Rizzoli SO, Westphal V, Jahn R, Hell SW. STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis. Nature 2006 440 935-939. 

It is now well established that in vivo efficient membrane fusion requires the interaction of small cytoplasmically exposed membrane proteins called soluble N-ethylmaleimide sensitive factor (NSF) attachment receptors (SNAREs) (Sollner et al., 1993). For synaptic vesicle exocytosis, the relevant SNAREs are synaptobrevin/ vesicle-associated membrane protein (VAMP) 1 and 2, syntaxin 1, and synaptosome-associ-ated protein of 25,000 daltons (SNAP-25). Synaptobrevins/ VAMPs are localized primarily on synaptic vesicles, while syntaxin and SNAP-25 are localized primarily on the plasma membrane. Fusion is driven by the progressive zippering of vesicle and plasma membrane SNAREs forming a four-helix bundle (Sutton et al., 1998). Although many other proteins appear to play critical roles in synaptic vesicle exocytosis, it seems likely that SNAREs are the minimal machinery required for fusion (Weber et al., 1998). Once assembled, SNARE complexes are disassembled by NSF, which functions in conjunction with SNAP proteins. 

Gad H, Low P, Zotova E, Brodin L, Shupliakov O (1998) Temporal dissociation between Ca " -induced synaptic vesicle exocytosis and clathrin-mediated endocytosis in a central synapse. Neuron 27 667-677. 

Missler, M, Zhang, W, Rohlmann, A, Kattenstroth, G, Hammer, RE, Gottmann, K and Sudhof, TC (2003) Alpha-neurexins couple Ca2-t channels to synaptic vesicle exocytosis. Nature 423 939-948. 

By contrast, tetanus toxin primarily has a central action it is transported in retrograde fashion up the motor neuron to its soma in the spinal cord. From there the toxin migrates to inhibitory neurons that synapse with the motor neuron and blocks exocytosis in the inhibitory neuron. The block of release of inhibitory transmitter gives rise to tetanus or spastic paralysis. The toxin from the venom of black widow spiders (a-latrotoxin) binds to neurexins, transmembrane proteins that reside on the nerve terminal membrane, resulting in massive synaptic vesicle exocytosis. 

The LMWG proteins associated with the parietal cell membranes appear to belong to the Rab (Ras-related rat brain) subgroup. Rab peptides, particularly Rab 3a, have been implicated in synaptic vesicle exocytosis, release of histamine... 

Darios F, Wasser C, Shakirzyanova A, et al. Sphingosine facilitates SNARE complex assembly and activates synaptic vesicle exocytosis. Neuron. 2009 62(5) 683-694. 

Neurotoxin A Blocks Synaptic Vesicle Exocytosis but Not Endocytosis at the Nerve Terminal. 1999, 147 1249-1260. 

Gaffield, M. A. Betz, W. J. Imaging synaptic vesicle exocytosis and endocjdosis with FM dyes. Nat. Protoc. 2006,1, 2916-2921. 

Petrenko, A.G., Perin, M.S, Davletov, B.A., Ushkaryov, Y.A., Geppert, M., and Sudhof, T.C., 1991, Binding of synaptotagmin to the a-latrotoxin receptor implicates both in synaptic vesicles exocytosis. Nature 353, 65-68. 

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