1. Unit 1 Cell and Molecular Biology Section 7 Signalling

2. Cell Signalling Cells do not work in isolation but continually ‘talk’ to each other by sending and receiving chemical signals to each other. This process is known as cell signaling Cell signaling has a number of important steps A signaling cell produces a signal molecule The signal molecule is recognised by a target cell by means of a receptor protein The receptor protein performs the first step in a series of transduction processes by converting the incoming extra-cellular signal to an intracellular signal that directs the cells behaviour

3. Principals Of Cellular Signalling Extracellular signal molecule A - IN Intracellular signal molecule B - OUT Change of molecule from A-B is an example of SIGNAL TRANSDUCTION Receptor protein ‘recognises’ signal molecule * * - this receptor protein may be on cell surface or inside cell

4. Signal molecules may be hydrophilic in nature ( e.g peptide hormones and neurotransmitters) or hydrophobic in nature (e.g. steroid hormones) Hydrophilic and hydrophobic signal molecules cross cell membranes by two different routes.

5. Hydrophobic signal molecules Hydrophobic signal molecules include steroid hormones such as cortisol, oestrogen (estradiol), progesterone and testosterone and thyroid hormones such as thyroxine. Steroid hormones diffuse directly through the cell membrane and bind to an inactive intracellular receptor protein known as a gene regulatory protein located in the cytosol or in the nucleus. On binding the intracellular receptor becomes active allowing it to bind to the equivalent regulatory sequence in the DNA

6. Nuclear membrane Activated Gene regulatory protein- steroid complex moves into nucleus DNA Activated receptor- steroid complex binds to the regulatory region of the target gene and activates transcription Activated target gene TRANSCRIPTION RNA Cortisol Plasma membrane Intracellular Gene Regulatory Protein Intracellular gne regulatory protein is activated by slight change in shape (not shown) The Effect Of Cortisol On Target Cells

7. Hydrophilic signal molecules Hydrophilic signal moleculespeptide hormonesneurotransmitters Hydrophilic signal molecules such as peptide hormones and neurotransmitters. These cannot pass through a cell membrane and must activate the surface receptor proteins Once activated the surface receptor protein generates an intracellular response This process is called signal transduction

8. The mechanism by which hydrophilic extra- cellular molecules such as peptide hormones generate an intracellular response Target cell Endocrine cell Receptor Bloodstream

9. Hormones endocrine glands Hormones, such as peptide hormones, are produced in endocrine glands, secreted into the bloodstream and carried throughout the body. These signal molecules only produce a response in target molecules with the appropriate surface receptor. This type of cell signalling is used by the body to co- ordinate the bodies metabolism and causes relatively slow, long lasting changes. Important peptide hormone include insulin and glucagon

10. A second group of hydrophilic signalling molecules are neurotransmitters An electrical signal is passed along a nerve and on reaching the terminal point stimulates the release of neurotransmitter signalling molecules. These diffuse across the gap between nerves known as a synapse and lock onto receptors found on the surface of the nearest nerve generating an electrical impulse Neurotransmitters produce a fast acting, short lived response between nerves

11. The mechanism by which hydrophilic extra-cellular molecules such as neurotransmitters generate an intracellular response DendronCell body Axon Neuron consists of dendron + cell body + axon Direction of nerve impulse Target cell Synapse showing movement of neurotransmitt er molecules Receptor When activated by signals from the surroundings, or other nerve cells, the neuron sends electrical impulses along its axon at speeds of up to 100 meters/second. On reaching the axon terminal, the intracellular electrical signals are converted to an extra-cellular form: each electrical impulse stimulates the terminal to secrete a pulse of chemical signal called a neurotransmitter. Neurotransmitters diffuse across the narrow gap, known as a synapse, and bind to receptors on the surface of the target cell

12. In both cases above the extracellular signal molecule binds to cell surface receptors as the hydrophilic molecules cannot cross the lipid bilayer. These receptors act as transducers which convert the signal on the outside of the cell to an intracellular signal There are three main classes of cell- surface receptors

13. Three types of signal transduction mechanism: ion channels enzyme-linked G-protein-linked Transport ions rapidly across membranes. Very important in Muscles and nerves Extracellular signal binds to inactive form and activates the enzyme function at the cytosol side G-linked protein actives G-protein which in turn starts sequence of intracellular events

14. Class1 - Ion-channel receptors. These are found on the surface of muscles and nerves and tranduce a signal in the form of a neurotransmitter into an electrical voltage. Class 2 - G-protein-linked receptors Class 2 - G-protein-linked receptors. This is the largest group. G-protein-linked receptors activate a G-protein which sets off a chain of events within the cell. These are found in all cells Class 3 - Enzyme linked receptors Class 3 - Enzyme linked receptors. An enzyme linked receptor binds an extracellular signal molecule switching on an enzyme activity, usually a kinase. on the other side of the membrane. This kinase activity causes the phosphorylation of other intracellular proteins. These are found in all cells

15. G-protein-linked receptors

16. The peptide hormone glucagon sets off a chain of reactions as follows:- Glucagon molecule binds to G-linked protein Inactive G-Protein is switched on by addition of phosphate to GDP Activated G protein binds to enzyme adenylate cyclase (AC) Enzyme AC breaks down ATP to cyclic AMP Cyclic AMP causes intracellular effect e.g. breakdown of glycogen or fats or activates gene regulatory proteins which switch on genes

17. Activity Read DART pg 70 – 72 Scholar 7.2 – 7.3 (7.1 to a lesser extent) Draw a diagram / make a poster to explain the steps in extracellular hydrophobic signalling Draw flow charts to show the processes in extracellular hydrophilic signalling http://www.sp.uconn.edu/~bi107vc/images/ani m/SigtranRA.gif http://www.sp.uconn.edu/~bi107vc/images/ani m/SigtranRA.gif