Synapse protein release

Figure 17.1. Neurotransmission (specific case of peptidergic cells). Production of the peptides in the cel I body (1). Packing of the peptides i nto large dense core vesicles for further transport to the axons (2). Release of neuropeptides from the cell soma (3) dendrites (4) and outside of the synapse (5). Release of classic neurotransmitters in the synaptic cleft (6). G-protein-coupled type receptors, which act as peptide receptors. (See color insert.)...

Synaptic Transmission. Figure 1 Synaptic transmission. The presynaptic terminal contains voltage-dependent Na Superscript and Ca2+ channels, vesicles with a vesicular neurotransmitter transporter VNT, a plasmalemmal neurotransmitter transporter PNT, and a presynaptic G protein-coupled receptor GPCR with its G protein and its effector E the inset also shows the vesicular H+ pump. The postsynaptic cell contains two ligand-gated ion channels LGIC, one for Na+ and K+ and one for Cl-, a postsynaptic GPRC, and a PNT. In this synapse, released transmitter is inactivated by uptake into cells. 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

The synaptic vesicles dock with proteins on the neuronal membrane and release their contents through exocytosis. The neurotransmitters contained in the vesicles spill into the synapse and passively diffuse across. 

The amount of acetylcholine present in the synapse and the amount of time that it remains there are critical. For example, the venom of the black widow spider is highly neurotoxic. It contains a protein known as a-latrotoxin that elicits the release of massive amounts of acetylcholine at the neuromuscular junction. Too much of a good thing can be a serious problem. 

This conclusion is supported by the mechaiusm of action of imipramine. Once a neurotransmitter has been released into the synapse, there are two ways to terminate its action. The first is to degrade it to inactive products, by MAO for example. The second is to remove the neurotransmitter through reuptake into the presynaptic neuron. This mechaiusm is the predominant one for clearing the synapse of serotonin, norepinephrine, and dopamine. Specific proteins embedded in the neuronal plasma membrane mediate the reuptake of these monoamine neurotransmitters. Imipramine is a nonspecific monoamine reuptake inhibitor that is, it slows the reuptake of aU three of these monoamines, which enhances the activity of these neurotransmitters. This also suggests that a deficit in the activity of one or more of the monoamines underlies the problem of depression. 

When the creation of long-term memories— repeated stimulations interrupted by rest periods—was simulated in this preparation by repeated pulses of serotonin, anatomical changes occurred. Specifically, new synaptic connections were created. It is likely that there are two underlying components to formation of new synaptic connections. One is local protein synthesis in the nerve terminal and the other is CREB (cAMP response element binding) dependent transcription in the neuronal nucleus. Of course, serotoiun pulses also stimulated the release of glutamate. So now the question is how repeated pulses of serotonin are related to protein synthesis and formation of new synapses. 

Reuptake. The nerve cell that released the neurotransmitter also has what are called reuptake sites on its surface. These reuptake sites are actually transporter proteins that are specific to each type of neurotransmitter. They act like miniature vacuum cleaners to retrieve the neurotransmitter from the synapse. The neurotransmitter is removed from the synapse at the reuptake site and returned to the inside of the nerve cell s axon terminal. Although the reuptake process recycles the neurotransmitter molecules for future use, the process does, in fact, serve to terminate the current neurotransmitter signal. 

There is evidence that a number of closely related phosphoproteins associated with the synaptic vesicles, called synapsins, are involved in the short-term regulation of neurotransmitter release. These proteins also appear to be involved in the regulation of synapse formation, which allows the nerve network to adapt to long-term passage of nerve impulses. 

Exocytosis is a term referring to processes that allow cells to expel substances (e.g., hormones or neurotransmitters) quickly and in large quantities. Using a complex protein machinery, secretory vesicles fuse completely or partially with the plasma membrane and release their contents. Exocytosis is usually regulated by chemical or electrical signals. As an example, the mechanism by which neurotransmitters are released from synapses (see p. 348) is shown here, although only the most important proteins are indicated. 

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