Cell signalling

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Cell Signalling is the transfer of information, that controls the cell behaviour, whether from cell to cell, or from the environment to cell. Cell signalling is very vital to the survival of organisms as it provides means of communication among cells and tissues allowing them to work collaboratively in order to provide an appropriate response to physical or chemical changes in the environment both externally and internally[1].

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. Autocrine signalling secrete a signal into the interstitial fluid within the same tissue. The next longer pathway is Paracrine 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 a hormone, produced by an endocrine gland, these hormones move through the bloodstream to target cell receptors[2].

A signal molecule coming from either a long or short distance functions as a ligand by binding to a receptor. The receptor can be embedded in the cell membrane, as well as being located within the cell itself. Most intracellular receptors bind small, hydrophobic molecules, such as steroid hormones, thyroid hormones, retinoids and vitamin D[3]. This type of receptors is most common in the regulation of gene transcription. Meanwhile, the cell surface receptors are more diverse and are involved in other complex cellular processes. 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[4][5].

There are 5 stages in most signalling pathways:

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

The cellular responses initiated by the cell signalling process reach effector proteins:[6].


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 behaviour 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 the 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, oligomerization of the receptor chains allows autophosphorylation[7]. 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-protein linked receptors.

Different cells that respond in differnt ways to the same signalling molecule

Different cells, even though they have the same G-protein-coupled receptors, make different responses. For example, acetylcholone acts as a signallig molecule in pancreatic acinar cell and endothelial cell. The signalling pathway is the same in both cells: acetylcholone binds G-protein-coupled receptor, and that leads to activation of G-protein and PL-C; as a result 2nd messenger called IP3 is generated, that then binds to Ca channels releasing Ca ions. Ca ions then activate Calmodulin protein. Up to this point both pathways are the same so far. However, in endothelial cell nitric oxide synthase is activated and nitric oxide is synthesised. Nitric oxide secretion induces relaxation of smooth muscle cells. In contrast, in pancreatic cells protein kinase is activated, this leads to phosphorylation of proteins that cause secretory vesicles to fuse with membrane and this resulrs in secretion of enzymes, e.g a-amylase.

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 the 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 causes 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[8].

Effect of pertussis toxin

The whooping cough is an example of a disease caused by the disruption of G-protein in the cell-signalling pathway. The disease-causing bacteria, Bordetella pertussis, settles in the lungs after infection. It will produce pertussis toxin, a protein. The toxin affects the G-protein Gi, altering the alpha subunit. Gi inhibits adenylyl cyclase, so preventing the production of the secondary messenger cyclic AMP (cAMP) and the pathway will be disrupted - this mechanism stops cell signalling as a form of regulation. Due to the toxin, however, the Gi cannot be activated; hence, it can no longer inhibit adenylyl cyclase. As a result, adenylyl cyclase activation is prolonged, leading to severe coughing[9].


  1. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K et al. Molecular Biology of The Cell. 6th ed. New York: Garland Science, Taylor and Francis Group; 2015.
  2. Boundless. Forms of Signalling. Available from: https://www.boundless.com/biology/textbooks/boundless-biology-textbook/cell-communication-9/signaling-molecules-and-cellular-receptors-83/forms-of-signaling-380-11606/ [Cited: 14/11/2016]
  3. Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K et al. Molecular Biology of The Cell. 6th ed. New York: Garland Science, Taylor and Francis Group; 2015; Chapter 15, p.874-875
  4. Hardin, J. et al. (2011). Becker's World of the Cell. 8th ed. San Francisco: Pearson. p392-3.
  5. Alberts, B., Johnson, A. and Lewis, J. (2008). Molecular biology of the cell. 5th ed. New York: Garland Science, Taylor and Francis Group, pp.629
  6. Alberts, Johnson, Lewis, Raff, Roberts and Walter (2008) ‘Mechanisms of Cell Communication’, in Molecular Biology of the Cell, 5th Edition. 5th Edn. New York: Taylor and Francis, Inc.
  7. Alberts, Johnson, Lewis, Raff, Roberts and Walter (2008) ‘Mechanisms of Cell Communication’, in Molecular Biology of the Cell, 5th Edition. 5th Edn. New York: Taylor and Francis, Inc.
  9. Alberts B, Bray D, Hopkin K, Johnson A, Lewis J, Raff M, Roberts K, Walter P; Essential Cell Biology, the 4th Edition; New York: Garland Science, Taylor and Francis Group; 2014; Chapter 16, page 542
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