Synapse cell-surface receptors

FIGURE 12.3 Entry and retrograde transport of rabies virus in a peripheral neuron. After a bite by a rabid dog, rabies viruses are concentrated at the neuromuscular synapse and attracted by cell surface receptors (probably gan-ghosides) expressed by the neuron. The virus is endocyted in a vesicle. Two scenarios have been proposed to explain the retrograde transport of the virus across the axon. 1. The virus may remain in the vesicle, and this vesicle interacts with the transport protein dynein, which ensures the migration of the package toward the minus end of microtubules. 2. A variant of this process postulates that the virus loses its envelope, and its nucleocapsid is transported by dynein along the microtubules. 

The receptor for NGF is TrkA, a 140 kDa cell surface protein that specifically binds NGF, but not other neurotrophins [5, 6, 9]. TrkA is expressed on the neuronal cell body and on neuronal processes. In its action as a target-derived trophic factor, NGF is secreted within the target organ and it then binds to TrkA receptors present on the growing neuronal process or synapse. The NGF-TrkA complex is then internalized and subsequently translocated to the cell body by retrograde axonal transport. In those cells that respond to NGF through autocrine or paracrine mechanisms, the growth factor can bind to any of the widely distributed TrkA molecules on the neuronal membrane. 

The central release of ATP from dorsal horn synaptosomes was proven by White et al. (1985). Further studies (Sawynok et al., 1993) suggest that ATP can be released from central terminals of primary afferent neurons as well as from terminals of non-primary afferents within the dorsal horn and that ATP and GABA are cotransmitters at many synapses in the dorsal horn (Jo and Schlichter, 1999). After being released ATP acts on specific receptors, designated as P2 purinoreceptors, on the cell surface. 

Ti k receptor cell surface proteins that are involved in transducing the actions of neurotrophins to promote neuronal survival, proliferation, migration, axonal and dendritic outgrowth and patterning, synapse strength and plasticity, injury protection, as well as controlling the activity of ion channels and neuroh ansmitter receptors. 

Mammen AL, Huganir RL, O Brien RJ (1997) Redistribution and stabilization of cell surface glutamate receptors during synapse formation. J Neurosci 77 7351-7358. 

Neurotransmitter/Receptor Binding. At this point, the neurotransmitter chemical is free in the synapse (extracellular fluid) and drifts (diffuses) in all directions. Some of the neurotransmitter molecules float across the synapse and bind to receptors on the surface of the adjacent nerve cell. Each neurotransmitter has its own unique three-dimensional shape and binds with certain receptors but not others. The binding between a neurotransmitter and a receptor is similar to fitting a key into a lock. When the neurotransmitter binds the receptor, the signal has been passed to the neighboring nerve cell. This is the process of neurotransmission. 

Negative Feedback. Some of the neurotransmitter diffuses back to the surface of the nerve cell that released it. There are also receptors that tit the neurotransmitter here. When a neurotransmitter binds a receptor (called an autoreceptor) at the axon terminal of the nerve cell that released it, it tells the nerve cell that there s plenty of neurotransmitter already in the synapse. So don t release anymore This process is called negative feedback and is analogous to the way a thermostat works in your home to control room temperature. 

Although pheromones can be considered as a special form of odorants (scents), their actions, effects and functions have similarities to those of hormones. They bind to a specific receptor which then activates an effector system, which initiates an action potential. They bind to specific sensory cells, the neurones, in the olfactory epithelium, which is located on the roof of the nasal cavities. The epithelium consists of three types of cells, basal, supporting and sensory cells (neurones). The neurones are bipolar, that is they possess a single dendrite, which extends from the cell body to the surface of the olfactory epithelium, and an axon that forms a synapse with a nerve that transfers information to the olfactory centre in the brain. The epithelium is covered with a thick layer of mucus, in which the pheromones dissolve. The mucus contains proteins that bind the pheromone(s) for delivery to the olfactory receptors and then to remove them once they have been detected. 

The taste cells are situated in the lingual epithelium with the apical membrane exposed to the mucosal surface of the oral cavity and the basal surface in contact with the nerve [interstitial fluid] [FIGURE 10]. Within the basolateral surface are the nerves which respond to the chemestiietic stimulants, i.e. direct nerve stimulation. The microvilli at the apical membrane contain receptor proteins which respond to sweeteners, some bitters and possibly coolants. The olfactory cells are bipolar neurons with dendritic ends containing cilia exposed to the surface and axons linked to the brain, where they synapse in the olfactory bulb. The transfer of information from this initial stimulus-receptor interaction to the brain processing centers involves chentical transduction steps in the membrane and within the receptor cells. The potential chemical interactions at the cell membrane and within the cell are schematically outlined in FIGURE 10. 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

Fig. 16.2. The elementary processes at a chemical synapse, a) In the resting state, the nenrotrans-mitter is stored in vesicles in the presynaptic cell, b) An arriving action potential leads to influx of Ca into the presynaptic cell. Consequently, the vesicles fuse with the presynaptic membrane and the neurotransmitter is released into the synaptic cleft, c) The neurotransmitter diffuses across the synaptic cleft and binds to receptors at the surface of the postsynaptic cell. Ion channel and receptor form a structural unit. The ion channel opens and there is an influx of Na ions into the postsynaptic cell. Recychng takes place in the presynaptic cell and the vesicles are reloaded with neurotransmitter.

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