**8. Receptors and their specificity**

Cells are bombarded by signals all the time. It does not matter if it is a single-celled organism or a complex multicellular organism. Outside of the cell will be environmental factors such as salinity, pH, temperature, osmolarity, but on top of these will be the likely presence of compounds such as pheromones, hormones and cytokines. Therefore the cell has to be able to "decide" which it will recognise and mount a response to. The job of such a decision rests with the receptors that the cell has. If the cell synthesises the correct receptor and places it at the right place at the right time then the cell will be able to recognise and respond to the correct signal.

At the start of a practice session for an orchestra the conductor will arrive with all the scores for the piece of music which they intend to play. There will be a score for all the different instruments. The conductor generally has a score with all the parts, and s/he is like a cell which can recognise all the music. However, it would be a waste of time and effort to give such complex scores to all the musicians. Also it would make playing the music extremely unwieldy. With all the parts of the music on the score there is only a short section of notes on any page that can be seen and the musicians would be required to turn the page extremely often. This is fine for the conductor, but the musicians need to be playing, not turning pages. It would be a waste of time and effort for a cell to make all the receptors it is capable of making, that is, having the whole score. What would be the point of making a receptor for a protein hormone that it would never encounter? It would be a misuse of precious materials and space to synthesis such a receptor that will never be used. Therefore the conductor, just like an organism, ensures that each musician has the appropriate score, just with their own music to play.

This analogy can be taken further if the musicians themselves are thought of as receptors. What happens at the start of the practice session? The scores are handed out and each musician will look at the score and confirm that it is the right part, if only silently in their mind. A cello player will only wish to receive cello music: if they take violin music for example it will be in the wrong cleft and probably not able to be played. Violins not only have to get music for the violin but have the right one, being either in first or second violins. If a musician gets the wrong music they will not be able to use it and give the response that the conductor is hoping for. The musician will remain silent, even when they are supposed to be playing, like a cell receptor in the presence of the wrong ligand. It is not uncommon for musicians to return music and ask for the correct score like a receptor rejecting a ligand and leaving themselves free for the arrival of the correct ligand onto their music stand so cellular harmony can be obtained.

### **9. Single instruments playing a simple string of notes**

Cell signalling is often presented as a neat array of components all in a line, as depicted in Figure 6A. In fact Krauss said: "The classical view of signalling pathways has been that of sequential transmission of signals in a linear signalling chain". This would be like listening to solo instruments, playing a linear line of notes on a page. Some representations of cell signalling show little else, making the systems look simple and easy to understand. But just as we don't often listen to single instruments, unless listening to a sonata perhaps, cell signalling is also a complex mix of many players, all adding to the harmony at the same time. As Krauss goes on to point out, signalling is far more complicated (Krauss, 2008).

Fig. 6. Signalling pathways are often depicted as a single series of components in a line, akin to a single line of music (A). However, they are usually much more complex, more like several instruments all playing at the same time (B).

Therefore cell signalling should be thought of as a group of instruments and voices, all competing for attention at the same time. Perhaps it is more like depicted in Figure 6B. Just as in a musical group, not all these musicians need to be in action all the time, and in fact it could be rather boring if that was the case. But they will all be there on stage, awaiting their cue from the music, always ready for action, but only acting when needed. In a cell the situation is the same, many signalling components will be quiescent until they are drawn upon to play their role in the control of the cell.
