Vesicles small synaptic

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Figure 4.10 An electron micrograph of a terminal varicosity containing a large dense-core vesicle (LDCV), indicated by the arrow and many small synaptic vesicles (SSVs), some of which contain an electron dense core. Calibration mark 250 nM. (Figure kindly supplied by M. Fillenz)...

The supply of conventional neurotransmitters in small synaptic vesicles is replenished in nerve terminals by local synthesis, and many conventional neurotransmitters are recaptured after secretion. In striking contrast, neuropeptides are initially synthesized in the cell soma, sequestered within the lumen of the secretory pathway and transported down the axon while undergoing cleavages... 

Release is another area of difference conventional neurotransmitters are secreted from small synaptic vesicles (SSVs) after cytosolic [Ca2+] transiently reaches concentrations of 50-100 pmol/1, while peptides are released from LDCVs at lower concentrations of cytosolic [Ca2+] (Fig. 18-3). Conventional neurotransmitter release is thought to occur very close to the site of Ca2+ entry (see Chs 9,10), while neuropeptides are typically released at a distance from the site of Ca2+ entry (Fig. 18-4). Furthermore the Ca2+ that stimulates exocytosis from LDCVs may come from either internal stores or the extracellular fluid. Thus, the location of LDCVs relative to the site of Ca2+ influx has a very crucial impact on the intensity of stimulation necessary for secretion to occur. 

FIGURE18-4 Neuropeptides and conventional neurotransmitters are released from different parts of the nerve terminal. A neuromuscular junction containing both large dense-core vesicles (containing the neuropeptide SCP) and also small synaptic vesicles (containing acetylcholine) was stimulated for 30 min at 12 Hz (3.5 s every 7 s). Depletion of the small clear vesicles at the muscle face and of the peptide granules at the nonmuscle face of the nerve terminal was observed. After stimulation, there was an increase in the number of large dense-core vesicles within one vesicle diameter of the membrane. (Adapted from reference [37].)... 

In other examples, the amount of peptide available for release can be depleted by repeated firing of a terminal since new peptide must arrive by axonal transport, while new conventional neurotransmitters are synthesized or recaptured locally and transported into small synaptic vesicles. 

Ahnert-Hilger G, Schafer T, Spicher K, Grund C, Schultz G, Wiedenmann B (1994) Detection of G-protein heterotrimers on large dense core and small synaptic vesicles of neuroendocrine and neuronal cells. Eur J Cell Biol 65 26-38... 

Vesicle Small membrane-walled containers (50 nm diameter) present at the presynaptic terminal of the neuron in which neurotransmitters are stored and from which neurotransmitters are released into the synaptic cleft... 

Many neurotransmitters are packaged into small synaptic vesicles 50 nm in diameter. These may originate from large endosomes rather than from the Golgi. They are usually recycled and refilled repeatedly386 Secretion of hormones, and of some neurotrans-... 

Synaptic vesicles can be isolated in large quantities. Their composition is well known, and the proteins have been studied intensively. Indeed, much of what we know about exocytosis and vescular transport has been learned from investigation of synaptic vesicles.554 561 562 A small synaptic vesicle of 35 nm diameter will contain -10,000 phospholipid molecules in its membrane and only about 200 protein molecules, at least one of which must be a 13-subunit vacuolar type proton pump (Fig. 18-14). This pump acidifies the vacuole, allowing uptake of a neurotransmitter. Although many different proteins may be found in synaptic membranes, only about 15, which are listed in Table 30-6, are found in all synaptic vesicles and appear essential to function. 

In neurons, the Ca2+-independent secretion is restricted to small synaptic vesicles, as demonstrated by synaptosomal and NMJ experiments, where glutamate, GABA, and acetylcholine are released in the absence of Ca2+, while catecholamines or peptides are not (Matteoli et al. 1988 Davletov et al. 1998 Khvotchev et al. 2000). Ca2+-independent release does not normally occur in endocrine cells (Grasso et al. 1980 Michelena et al. 1997 Silva et al. 2005), although in some cultured cells it does (Meldolesi et al. 1983 Lang et al. 1998 Tse and Tse 1999). 

Beaumont V, Zucker RS (2000) Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels. Nat Neurosci 3 133 41 Beech DJ, Bernheim L, Hille B (1992) Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons. Neuron 8 97-106 Benfenati F, Bahler M, Jahn R et al (1989a) Interactions of synapsin I with small synaptic vesicles distinct sites in synapsin I bind to vesicle phospholipids and vesicle proteins. J Cell Biol 108 1863-72... 

Giovedi S, Darchen F, Valtorta F et al (2004a) Synapsin is a novel Rab3 effector protein on small synaptic vesicles. II. Functional effects of the Rab3 A-synapsin I interaction. J Biol Chem 279 43769-79... 

Wiedemann C, Schafer T, Burger MM et al (1998) An essential role for a small synaptic vesicle-associated phosphatidylinositol 4-linase in meurotransmitter release. J Neurosci 18 5594-5602 Wierda KD, Toonen RF, de WH et al (2007) Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron 54 275-90 Willars GB (2006) Mammalian RGS proteins multifunctional regulators of cellular signalling. Semin Cell Dev Biol 17 363-76... 

Small synaptic vesicles (<25 nm radius) Small SLMV (30-50 nm radius)... 

Landen M, Davidsson P, Gottffies CG, Grenfeldt B, Stridsberg M, et al. 1999. Reduction of the small synaptic vesicle protein synaptophysin but not the large dense core chro-mogranins in the left thalamus of subjects with schizophrenia. Biol Psychol 46 1698-1702. 

Local modulation through the dendritic release of DA occurs in both the SN and the VTA. Ultrastructural observations have been made with immunolocalization of the vesicular monoamine transporter-2 as marker for sites of intracellular monoamine storage within SN and VTA dopaminergic neurons identified by TH immunoreactivity (Nirenberg et al., 1996a). This study has reported that DA is stored in and may be released from dendritic small synaptic vesicles or large dense-core vesicles, while the smooth endoplasmic reticulum represents the main site for the DA storage. 

Protease-free preparations of TeTx and BoNT/B, D, F and G cleave a membrane protein of small synaptic vesicles (SSV) called VAMP or synaptobrevin (Schiavo ef ai, 1992 a, 1993 a,c, Yamasaki et ai, 1994 a, b). Conversely, BoNT/A, C and E act on proteins associated with the presynaptic membrane BoNT/A and E cut SNAP-25, while serotype C cleaves syntaxin, in addition to SNAP-25 (Blasi efai, 1993 a, b ... 

The procedure for the preparation of synaptosomes and small synaptic vesicles (SSV) from rat brain cortex follows established methods with minor modifications (Schiavo and Montecucco, 1995). 

Acidification of Small Synaptic Vesicles in SLO-Permeabilized Synaptosomes... 

Fig. 2. Acidification of small synaptic vesicles by glutamate and chloride in synap-tosomes. The acidification assay was performed as described in section 3.2 of this chapter. Two representative experiments with intact (upper trace) or SLO-permeabilized (lower trace) synaptosomes are shown. The ordinate gives the changes of absorbance obtained (A 492-530). Final concentrations of potassium glutamate (Glut), KCl, and ammonium sulfate (NH/) were 10 mM, 45 mM and 30 mM, respectively. The uptake of glutamate and chloride result in an acidification of the lumen of small synaptic vesicles, which increases the vesicular uptake of acridine orange, resulting in a decrease in the amount of extravesicular dye. This acidification can be only observed when the plasma membrane is permeabilized...

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