Synaptic vesicle proteins

Tetanus is a disease caused by the release of neurotoxins from the anaerobic, spore-forming rod Clostridium tetani. The clostridial protein, tetanus toxin, possesses a protease activity which selectively degrades the pre-synaptic vesicle protein synaptobrevin, resulting in a block of glycine and y-aminobutyric acid (GABA) release from presynaptic terminals. Consistent with the loss of neurogenic motor inhibition, symptoms of tetanus include muscular rigidity and hyperreflexia. The clinical course is characterized by increased muscle tone and spasms, which first affect the masseter muscle and the muscles of the throat, neck and shoulders. Death occurs by respiratory failure or heart failure. 

As noted above, synaptic vesicles are not typically generated at the level of the TGN. Instead, they are assembled from endocytosed material retrieved from the synaptic plasma membrane. Synaptic vesicle and plasma membrane lipids and proteins are synthesized in the endoplasmic reticulum and modified in the Golgi apparatus, where they are then packaged in secretory vesicles. These synaptic precursors are delivered to the plasma membrane from the cell body by the constitutive secretory pathway. Synaptic vesicle proteins must be retrieved by clathrin-mediated synaptic vesicle endocytosis, a variant of RME with some neuron-specific components. Once the vesicle sheds its clathrin coat, the uncoated vesicle fuses with a... 

TABLE 9-2 A glossary of proteins in the synapse [73,74] 1. Synaptic vesicle proteins... 

Levetiracetam s activity may be related to its binding to the synaptic vesicle protein SV2A. 

Lynch BA et al The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A 2004 101 9861. [PMID 15210974]... 

Detection of Synaptic Vesicle Exocytosis and Endocytosis UsingpHluorin-Tagged Synaptic Vesicle Proteins... 

Fig. 3 Synaptophysin-pHluorin is a fusion construct of the synaptic vesicle protein synaptophysin (a four-transmembrane domain synaptic vesicle protein) with a pH-sensitive EGFP at its C-terminal (located in the synaptic vesicle lumen). Synaptic vesicle lumen normally has an acidic pH of approximately 5.5 at which spH fluorescence is quenched. When vesicles fuse, lumenal EGFP is exposed to the extracellular pH, which results in a marked increase in its fluorescence. During endocytosis, pHluorin fluorescence is re-quenched as vesicle lumen becomes acidic.

Virmani T, Han W, Liu X, Sudhof TC, Kavalali ET (2003) Synaptotagmin 7 splice variants differentially regulate synaptic vesicle recycling. EMBO J 22 5347-57 Voglmaier SM, Kam K, Yang H, Fortin DL, Hua Z, Nicoll RA, Edwards RH (2006) Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling. Neuron 51 71-84... 

Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH (1994) Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci 14 5223-5235. 

Bajjalieh SM, Peterson K, linial M, Scheller RH (1993) Brain contains two forms of synaptic vesicle protein 2. Proc Natl Acad Sci USA 90 2150-2154. 

Bajjalieh SM, Peterson K, Shinghal R, Scheller RH (1992) SV2, a brain synaptic vesicle protein homologous to bacterial transporters. Science 257 1271-1273. 

Crowder KM, Gunther JM, Jones TA, Hale BD, Zhang HZ, Peterson MR, Scheller RH, Chavkin C, Bajjalieh SM (1999) Abnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci USA 96 15268-15273. 

Custer KL, Austin NS, Sullivan JM, Bajjalieh SM (2006) Synaptic vesicle protein 2 enhances release probability at quiescent synapses. J Neurosci 26 1303-1313. 

Feany MB, Lee S, Edwards RH, Buckley KM (1992) The synaptic vesicle protein SV2 is a novel type of transmembrane transporter. Cell 70 861-867. 

Janz R, Hofmann K, Sudhof TC (1998) SVOP, an evolutionarily conserved synaptic vesicle protein, suggests novel transport functions of synaptic vesicles. J Neurosci 18 9269-9281. 

Pyle RA, Schivell AE, Hidaka H, Bajjalieh SM (2000) Phosphorylation of synaptic vesicle protein 2 modulates binding to synaptotagmin. J Biol Chem 275 17195-17200. 

Schivell AE, Batchelor RH, Bajjalieh SM (1996) Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin. J Biol Chem 271 27770-27775. 

Hiding H, Scheller RH (1996) Phosphorylation of synaptic vesicle proteins modulation of the alpha SNAP interaction with the core complex. Proc Natl Acad Sci USA 93 11945-9 Hirokawa N, Sobue K, Kanda K et al (1989) The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1. J Cell Biol 108 111-26 Ho MF, Bahler M, Czernik AJ et al (1991) Synapsin I is a highly surface-active molecule. J Biol Chem 266 5600-7... 

Signal transduction was studied most precisely for the 5-HTiA receptor in rat amygdala (Koyama et al. 1999). The receptor operated through a N-methyl maleimide-sensitive mechanism and by adenyl cyclase inhibition rather than any change in K+ or Ca2+ channels. The fall in cyclic AMP presumably was followed by decrease in the phosphorylation of synaptic vesicle proteins and, finally, in a decrease of exocytosis. 

---