Cell signalling

Cell Signalling is the transfer of information, that controls the cell behaviour, whether from cell to cell, or from environment to cell.

There are many different types of cell signalling that vary immensely. About 10-15% of the genome codes for the creation of these cell signalling molecules. Most signals involved are chemicals but some can be physical signals such as light.

Different signalling mechanisms are used depending on how far the signal needs to travel. For short distances, there is a pathway between adjacent cells and takes place via a gap junction. The pathway sizes increase from gap junction, to contact dependant, where the signal is displayed on the surface and a receptor on another cell surface, for example, an immune response cell. Paracrine pathways secrete a signal into the interstitial fluid within the same tissue. The next longer pathway is Autocrine signalling and Synaptic signalling. The longest signalling pathway, which usually has the longest response time to the stimulus is Endocrine signalling, where the signal is secreted into the blood stream which flows around the body.

A signal molecule coming from either a long or short distance functions as a ligand by binding to a receptor. The ligand is the 'primary messenger', and its binding to the receptor often causes additional molecules inside the cell to receive the signal. These are known as 'second messengers' and they relay the signals to different parts of the cell, initiating a cascade of changes (to behaviour or gene expression) within the receiving cell.

There are 5 stages:

1. Signal
2. Reception
3. Transduction
4. Amplification
5. Response
   

The cellular responses initiated by the cell signalling process reach effector proteins:

• metabolic enzymes which lead to altered metabolism
• gene regulatory proteins which lead to altered gene expression
• cytoskeletal proteins which lead to altered cell shape or movement
  

Cell Surface Receptor Proteins

There are three main classes of cell-surface receptor proteins: 

1. Ion-channel Coupled Receptors
2. G-Protein Coupled Receptors
3. Enzyme-Coupled Receptors

These cells surface receptors act as signal transducers by converting extracellular ligand-binding into intracellular signals. These signals ultimately alter the behavior of the cell. In Ion-channel coupled receptors, there is rapid synaptic signalling between nerve cells and electrically excitable cells e.g.muscle and nerve cells. This signal is mediated by few neurotransmitters which are transiently opening and closing ion channels. The protein to which the signal binds forms this ion channel which the signal alters the permeability of in order to change the excitability of the postsynaptic target cell. In G-Protein coupled receptors there is an indirect regulation of activity of a plasma-membrane bound protein targeted as an enzyme or ion channel. There is an interaction between the target protein and an activated receptor, mediated by the G-protein which activates a change in concentration of intracellular mediators OR a change in the ion permeability of the membrane. Enzyme-coupled receptors have two ways of working. Either they can function directly as enzymes, or link directly with enzymes which they activate. They have their ligand-binding sites outside the cell as they are in most cases single-pass transmembrane proteins. The majority of the enzyme-coupled receptors are either protein kinases or associates of. These phosphorylate specific sets of proteins (when activated) in the target cell. Enzyme-coupled receptors can also exhibit intrinsic kinase activity in order to activate the appropriate secondary messenger. An example of this can be seen in the receptor tyrosine kinases, binding of the ligand to enzyme linked receptor leads to cross-linkage of the two receptor chains, oligomerisation of the receptor chains allows autophosphorylation.   G-protein receptors are transducers in the signalling pathway, ie they convert a signal from one to another. G-protein receptors can be divided into 2 types, the first being Monomeric G-protein that transduces signals from enzyme linked receptors. The other is Trimeric G-protein which transduces signals from G-proteine linked receptors. 

The effect of cholera on cell signalling

Cholera toxin binds to and enters only cells that have GM1 on their surface, including epithelial cells. Its entry into a cell leads to the prolonged activation of adenylyl cyclase which results in the constant production of intracellular cAMP leading to very high concentrations of cAMP in the cell. This results in opening of the CFTR channel which allows Cl- water into the large intestine which sets up an electrical gradient that draws Na+ back into the intestinal lumen. This causses an increase in NaCl concentration inside the lumen which draws water into the intestine. This therefore causes diarrhoea and dehydration. Cholera toxin can also have positive effects on cells in certain specific cases. The toxin has been found to produce adjuvant effects as well as immunomodulatory effects.