Getting the Message

1. Getting the Message Signals & their transduction

2. Signalling Molecules • The endocrine and nervous system transmit messages by releasing signalling molecules, hormones & neurotransmitters that act by attaching to specific receptors (enzyme-like protein molecules) in the membranes of target cells. • A target cell is one that has the appropriate receptor for a particular signalling molecule and can be reached by that molecule. • Some target cells may be widespread throughout the body (as in the target cells for thyroxine) or may be located in a particular place (as in the hormones released from the hypothalamus that act on certain cells in the pituitary gland.

3. Hydrophobic & hydrophillic signals • Hydrophillicsignalling molecules • Neurotransmitters • Growth Factor Hormones • Insulin • Hydrophobic signalling molecules • Steroid Hormones • Thyroid Hormones

4. Binding specificity • Signalling molecules are called ligands Signal Signal • High binding specificity between the ligand and the receptor is due to complementary groups of atoms and shapes Receptor molecule

5. Receptors for hydrophillicsignalling molecules Small Peptides Vasopressin Protein hormones made up of chains of amino acids. Some with carbohydrate side chains. Insulin Glucagon Growth Hormone Luteinizing hormone Neurotransmitters Hormones derived from specific amino acid molecules; tyrosine and tryptophan Adrenaline Dopamine • Water soluble hormones are unable to pass through the cell membrane. As a result they bind with specific receptors on the surface of cell membrane of the target cell. They are all amino acid based molecules but vary in the number of amino acid residues. Water soluble hormones are stored in vesicles and secreted from the cell by exocytosis Secretory Cell Receptor on plasma membrane Target Cell

6. Where are the receptors for hydrophobic signalling molecules? • These hormones are able to pass directly through the plasma membrane and bind their specific receptor (intracellular) within the cytoplasm of the target cell. These molecules require a carrier protein for transport in the blood as it is water based. Steroids Cortisol Testosterone Oestrogen Progesterone Eicosanoids (derived from fatty acids) Prostoglandins Lipid soluble hormones leave the secretory cell by simple diffusion Target cell Intracellular receptor

7. Signal Transduction Fatty Acid based Hormones (lipid soluble) Protein based Hormones (water soluble)

8. Types of plasma membrane bound receptors Ion Channel Receptor G protein-coupled Receptor Tyrosine kinase linked Receptor Milliseconds Seconds Can take hours Binding of ligand causes a shape change that opens the channel so ions can enter or leave the cell. Eg. Acetylcholine at nerve/muscle junctions. Binding of ligand activates a G protein which activates or inhibits an enzyme or modulates an ion channel that generates secondary messengers. Eg. Receptor for glucagon Binding of ligand to TK causes a shape change that activates enzymes within the cell Eg. Human Growth Factor

9. The Signal Transduction Pathway Applying the stimulus response model. 1.Signal binds to receptor molecule. 2. Receptor molecule changes shape of confirmation. 3. Initiates a molecular cascade of secondary messenger molecules to an effector molecule. 4.Effector initiates the cellular response. 1.Signal binds to receptor 3.Effector molecule opens ion channels. The cellular response is to allow entry of substance. 2. Successive molecules relay the signal to a final effector molecule. This is signal transduction.

10. How is the signal amplified? • Each successive step in the signal transduction pathway may activate multiple molecules in the next step. • Pathways may branch to produce multiple responses from the initial signal. • This is why small amounts of signalling molecules can produce a significant response or even multiple responses.

11. Hydrophobic signals bind to intracellular receptors Steroid hormones regulate gene expression. Steroid Hormone moves across the plasma membrane. Ligand-Receptor complex Signal binds with intracellular protein receptor. The ligand-receptor complex moves into nucleus to bind with DNA to regulate gene expression. Proteins are the products of gene expression. Transcription Translation

12. Activate or inhibit enzyme action. Regulate the expression of proteins by switching genes on or off. Move transport vesicles to the plasma membrane to secrete cellular products. Open or close protein channels. Four Cellular Responses Effector molecules bring about the cellular response. Once a signalling molecule has delivered the message to a cell and the cell response is initiated, the signalling molecule is degraded by enzymes.