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... 

In the classic model of synaptic vesicle recycling in nerve terminals, synaptic vesicles fuse completely with the plasma membrane and the integrated vesicle proteins move away from the active zone to adjacent membrane regions (Fig. 9-9A). In these regions, clathrin-mediated synaptic vesicle endocytosis takes place rapidly after neurotransmitter release (within seconds) [64]. The process starts with the formation of a clathrin-coated pit that invaginates toward the interior of the cell and pinches off to form a clathrin-coated vesicle [83]. Coated vesicles are transient organelles that rapidly shed their coats in an ATP/chaperone dependent process. Once uncoated, the recycled vesicle fuses with a local EE for reconstitution as a synaptic vesicle. Subsequently, the recycled synaptic vesicle is filled with neurotransmitter and it returns to the release site ready for use. This may be the normal pathway when neurotransmitter release rates are modest. Clathrin/ EE-based pathways become essential when synaptic proteins have been incorporated into the presynaptic plasma membrane. 

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]... 

Deperthes D, Frenette G, Brillard-Bourdet M, et al. Potential involvement of kallikrein hK2 in the hydrolysis of the human seminal vesicle proteins after ejaculation. J Androl... 

Lilja H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 1985 76 1899-1903. 

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... 

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