Vesicle nerve terminal associated proteins

Amphiphysin Nerve-terminal protein that associates with synaptic vesicles probably via AP2 bound to synaptotagmin. May function in endocytosis. 

Subtypes of Rab, particularly Rab3, have been implicated in the regulation of exocytosis and neurotransmitter release at nerve terminals (see also Chs 9 and 10) [30,31]. One possible scheme by which this might occur is shown in Figure 19-5. In its GTP-bound form, Rab associates with synaptic vesicles and interacts with other membrane proteins to create a complex unfavorable for vesicle docking and perhaps fusion. Upon depolarization of the nerve terminal, a Rab GAP is activated, which results in dissociation of the GDP form of Rab from the vesicle membrane. This enables the synaptic vesicle to proceed with... 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

Figure 16.3 Neurotransmitter release, (a) Presynaptic nerve terminal containing vesicles and other organelles, (b) Neurotransmitter-containing vesicles are made of lipid bilayers. Associated proteins participate in the release process, (c) The vesicle associates with the presynaptic membrane via protein complexes that mediate release, (d) Release of neurotransmitter into the synapse is by protein-mediated fusion of vesicle and presynaptic membranes.

Stimulus-evoked, calcium-dependent release of acetylcholine (ACh) from the cholinergic synapse normally occurs through the formation of a fusion complex between ACh-containing vesicles and the intracellular leaflet of the nerve terminal membrane (Amon et al., 2001). This synaptic vesicle fusion complex consists of several proteins of the SNARE family, including a 25 kDa synaptosomal associated protein (SNAP-25), vesicle-associated membrane protein (VAMP, or synaptobrevin), and the synaptic membrane protein syntaxin. Other SNARE proteins have been identified as components of membrane transport systems in yeast and mammals but have not been implicated as targets for BoNTs. Meanwhile, type A and E neurotoxins cleave SNAP-25 while types B, D, F, and G act on VAMP and type C1 toxin cleaves both syntaxin and SNAP-25. Neurotoxin-mediated cleavage of any of these substrates disrupts the processes involved in the exocytotic release of ACh and leads to flaccid paralysis of the affected skeletal muscles. 

Huttner, W., et al. (1983). Synapsin I (Protein I), a Nerve Terminal-specific Phosphoprotein. Ill Its Association with Synaptic Vesicles Studied in a Highly Purified Synaptic Vesicle Preparation, J. Cell Biol. 96 1374-1388. 

Along with ion channel activity, protein phosphorylation plays a fundamental role in regulating the release of neurotransmitters from synaptic terminals. A protein selectively associated with vertebrate nerve terminals, synapsin I, may be particularly important in this respect. Strong experimental evidence indicates, in fact, that the state of phosphorylation of this protein participates in regulating the number of neurotransmitter-containing vesicles that are immediately available for exocytosis. ... 

---