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COMMUNICATION WITHIN MULTICELLULAR ORGANISMS This topic will look at 3 areas • Coordination • Hydrophobic signals and control of transcription. • Hydrophilic signals and transduction. Coordination in animals is produced through nervous transmission and hormonal secretion. Comparing the 2 systems electrical impulse and extracellular signalling molecules along neuron axons extracellular signalling molecules bloodstream cells with connections to neurons (effectors) almost any cells in the body Time for response faster slower Duration of response transient longer lasting Extent of response localised widespread Nature of signal Transmission of signals Target cells Coordination is important for homeostasis. What is homeostasis? What are the main features of homeostatic control? • Controlled system • Monitoring centre • Mechanisms of correction • Set point re-established Coordination allows humans to cope with physiological challenges Exercise What challenges does it bring? • • • • • Cardiovascular Ventilatory Metabolic Thermoregulatory Osmoregulatory EXTRACELLULAR SIGNALLING Signalling cells Specific signalling molecules released as a result of a change in internal state Signalling molecules carried to target cells Target cells Arrival of signalling molecules at target cells is linked to a change in the internal state of the cells (cell response) Feedback response may cause original cells to stop producing signalling molecules Different cell types produce specific signalling molecules. HOW DOES A TARGET CELL ‘KNOW’ THAT IT SHOULD RESPOND TO A SPECIFIC SIGNAL? Cells can only detect and respond to signals if they possess a specific receptor. Adrenaline Adrenaline receptor protein Insulin Insulin receptor protein Different cell types may show a specific tissue response to the same signal. Betareceptor Adrenaline Betareceptor Adrenaline Amylase release stimulated Glycogen breakdown stimulated Cell in mammalian salivary gland Cell in mammalian liver HYDROPHOBIC SIGNALS AND THE CONTROL OF TRANSCRIPTION HYDROPHILIC SIGNALS AND TRANSDUCTION What are hydrophobic signals and how are they involved in the control of transcription? • Hydrophobic signals can pass through membranes so their receptor molecules can be within the nucleus. • They can directly influence the transcription of genes. • They include the thyroid hormone thyroxine and steroid hormones General action of hydrophobic signalling molecules Hormone Intracellular receptor protein Altered rate of protein synthesis (long-lasting effects) Altered rate of gene transcription Thyroxine is a hydrophobic hormone that regulates the metabolic rate. Thyroxine is released from the thyroid gland. Thyroxine absent Thyroid receptor protein bound to DNA Transcription of Na+/K+ ATPase gene inhibited Thyroxine present Receptor protein undergoes conformational change Thyroxine Synthesis of Na+/K+ ATPase Transcription of Na+/K+ATPase gene More Na+/K+ATPases in cell membrane Insertion into membrane ATP degraded faster Increased metabolic rate Synthesis of Na+/K+ ATPase Transcription of Na+/K+ATPase gene Steroid hormones are hydrophobic signalling molecules. Animation of mechanism of steroid hormone action. The steroid hormone receptor proteins are transcription factors. Inactive transcription factor Inhibitory protein complex Hormone-binding site Steroid hormone Active transcription factor DNA-binding site exposed HYDROPHOBIC SIGNALLING MOLECULES CAN BIND TO NUCLEAR RECEPTORS TO REGULATE GENE TRANSCRIPTION. Animation of regulation of transcription. What are hydrophilic signals and how are they involved in the transduction of messages? • Hydrophilic signals need receptor molecules on the cell surface. • Transmembrane receptors change conformation (shape)when the ligand (messenger) binds to outside of the cell. • The signal molecule does not enter the cell. • The signal is transduced (passed) across the cell membrane. • This often involves cascades of G-proteins or phosphorylation by kinase enzymes. General action of hydrophilic signalling molecules Hormone (ligand) Receptor protein Signal transduction Cell responses (short-lasting effects) Examples include the peptide hormones ADH and insulin. These are made from short chains of amino acids. ADH Insulin Insulin regulates the glucose concentration of the blood Beta-cells in pancreas release more insulin Insulin transported in blood Insulin acts on adipose, liver and muscle cells Change detected Blood glucose concentration rises Blood glucose concentration at set point More glucose is taken up by cells Blood glucose concentration falls 1. Insulin binds to receptor 2. Kinase enzyme phosphorylates itself (autophosphorylation) 3. Receptor phosphorylates insulin receptor substrate (IRS-1) P P P P 4. Phosphorylated IRS-1 acts on effectors to trigger cell responses P Action of insulin on fat and muscle cells GLUT 4 Animation of insulin action. Exercise triggers recruitment of GLUT 4 An illness related to blood glucose is Diabetes Mellitus • A disease caused by defects in the insulin signalling system. • Two types of diabetes mellitus are recognised. Type 1 and Type 2 • What are the general symptoms of diabetes mellitus? Type 1 – Insulin dependant diabetes Cause Destruction of beta cells in pancreas by immune system Usual age of onset Childhood Nature of defect Pancreas does not produce any insulin Treatment Daily insulin injections and management of diet to control glu. Conc. Type 2 – Non-insulin Dependant diabetes Exact cause unknown Obesity is a risk factor Adulthood Target cells develop Insulin resistance. Loss of receptor function Eat less sugar and saturated fat. Regular exercise. Medication to lower Blood glu. Conc. Global prevalence of diabetes mellitus Numbers are millions! Terrestrial vertebrates require mechanisms for conserving water Thank goodness I can make ADH! ADH regulates the body’s water balance Pituitary gland releases more ADH ADH transported in blood Change detected Blood water concentration falls Blood water concentration at set point ADH acts on kidney collecting ducts More water reabsorbed into blood Less urine made Blood water concentration rises MECHANISM OF ACTION OF ADH Lumen of collecting duct Collecting duct cell Blood 2. ADH receptor H2O 1. ADH 5. Fusion of vesicles containing AQP2 water channel proteins 4. Protein phosphorylation 3. Activation of protein kinase A Aquaporins are protein channels that allow efficient transmembrane movement of water. Animation of water movement through an aquaporin channel. Aquaporins An illness related to ADH Diabetes insipidus • Disease in which the water conservation mechanism of the kidneys fails. • How could the system fail to work? • What might the symptoms of diabetes insipidus be? Symptoms of diabetes insipidus • Excessive thirst. • Production of large quantities of dilute urine (‘insipidus’ = lacks flavour). The two types of diabetes insipidus • Central diabetes insipidus: insufficient ADH is produced. • Nephrogenic diabetes insipidus: cells in the lining of the collecting duct are unable to respond to ADH. POSSIBLE CAUSES OF DIABETES INSIPIDUS Lumen of collecting duct Collecting duct cell Blood ADH receptor insensitive to ADH AQP2 No ADH Phosphorylated target proteins Protein kinase A Summary of ADH action • ADH binds to receptor in collecting ducts. • Recruitment of channel protein aquaporin 2 (AQP 2) • Water moves through aquaporins in membrane • Water is reabsorbed into blood • No ADH or insensitive receptor proteins leads to diabetes insipidus