Mechanism of Signal Transmission

The mechanism by which the activated receptor talks to the G-protein is only partially understood. Generally, the switch function of the receptor is considered in terms of allosteric conformational changes of the 7-hehx membrane bimdle (review Bourne, 1997). According to this representation, changes in the structure of the transmembrane bimdle are passed on to the cytoplasmic loops of the receptor. Communication with the a-subunit of the heterotrimeric G-protein takes place via these loops. 

The heterotrimeric G-protein, which exists as the inactive GDP form, now binds via its a-subunit to the activated receptor and is activated itself. An exchange of GDP for GTP takes place and the Pysubunit of the G-protein dissociates (see 5.5.3). Once the G-protein is activated, it frees itself from the complex with the receptor, which either returns to its inactive ground state or activates further G-proteins. 

The best investigated is the desensitization of the adrenaline receptor type P2 and of rhodopsin. Rhodopsin has the function of a light receptor in the process of vision, ft receives light signals and conducts them to the relevant G-protein, transducin. The key reaction in desensitization of both systems is the phosphorylation of the receptor at the cytoplasmic side by specific protein kinases. 

Two classes of protein kinases are involved in the phosphorylation and desensitization (review Freedman and Lefkowitz, 1996)  

Phosphorylation of the cytoplasmic domain of G-protein coupled receptors can take place via cAMP-dependent protein kinases, protein kinase A) or via protein kinase C (Chapter 7) (Fig. 5.8). This is a feedback mechanism the hormonal activation of the receptor leads, via G-proteins and adenylyl cyclase/cAMP, to activation of protein kinases of type A (see 5.6.1, 6.1 and Chapter 7). The activated protein kinases phos-phorylate the receptor in the region of the cytoplasmic domain on Ser/Thr residues (see Fig. 5.6). 

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Membrane-bound receptors are actually transmembrane proteins they display an extracellular domain linked to an intracellular domain by a transmembrane domain. Binding of a hormone to the extracellular side induces a specific reaction on the cytosolic side, which then triggers further reactions in the target cell. The mechanism of signal transmission over the membrane will be discussed in more detail in Chapters 5,... 

A physiologically important aspect of signal transmission via transmembrane receptors is its regulation. The cell has various mechanisms available, with the help of which the number and activity of transmembrane receptors can be regulated. The aim of... 

Not only specific adhesion but also controlled endo- and transcytosis of microorganisms into cells by bacterial adhesion is another potential development in bacterial adhesion. The mechanism follows signal transmission associated with the protein binding, which then triggers the intracellular translocation of the microorganism. This feature could be applied for controlled cellular binding and internalization to deliver compounds specifically to the interior of cells. ... 

The investigation of the rates of signal transmission in nerve fibre has already been quoted as an example of the ingenious experiments carried out by Helmholtz (see chapter 1). Outstanding biophysical investigations on the rate processes and electrochemical events, as well as on the chemical and ionic excitation mechanisms, have been carried out in the intervening 1 SO years. Much has been achieved recently by molecular biological techniques in the identification and production of components of receptor and channel proteins. Several of the kinetic techniques described in this and subsequent... 

Morphine may be administered orally, intravenously, or epidurally. An advantage of epidural administration is that it provides effective analgesia while minimizing the central depressant effects associated with systemic administration. The mechanism of action with the epidural route of administration involves opioid receptors on the cell bodies of first-order sensory neurons in the dorsal root ganglia as well as their axon terminals in the dorsal hom. Stimulation of these receptors inhibits release of substance P and interrupts transmission of the pain signal to the second-order sensory neuron. 

The molecular basis of most of these processes is not yet clear. Most of what we know concerns the absorption of quanta by the photoreceptor pigments, while stimulus transformation and signal transmission have as yet been investigated only in part and in a very few organisms. In blue-green algae, not even the movement mechanism is clear, so that any model of the motor response is highly speculative. 

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