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AH Biology: Unit 1 Communication Within Multicellular Organisms Communication within multicellular organisms - General principles. - Hydrophobic signals and control of transcription. - Hydrophilic signals and transduction. In animals communication is mediated by nervous transmission and hormonal secretion. Nervous communication Hormonal communication Nature of signal Electrical impulses Extracellular and extracellular signalling signalling molecules molecules Transmission of signal Along the axons of neurons Through the bloodstream Target cells Any cells with connections to neurons (effectors) Almost any cells in the body Time for response Faster to occur Slower Duration of response Longer lasting Transient Extent of response Localised Widespread Coordination is important for homeostasis Coordination allows integrated homeostatic responses to be made. Disturbances Coordinated responses Controlled system Monitoring centres Error signal Set point values Errorcorrecting mechanisms Coordination of responses allows animals to cope with physiological stress, eg a human doing exercise. . . Exercise • Cardiovascular challenge • Ventilatory challenge • Metabolic challenge • Thermoregulatory challenge • Osmoregulatory challenge 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) 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 (may also act as signalling cells) Arrival of signalling molecules at target cells is linked to a change in the internal state of the cells (cell response) Different cell types produce specific signalling molecules. Spatial organisation of signalling molecules Eukaryotic cell: 50 μm Distance: 1 nm 1 μm 1 mm 1m 1 km Animal pheromones Hormones Neurotransmitters 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 Amylase release stimulated Cell in mammalian salivary gland Betareceptor Adrenaline Glycogen breakdown stimulated Cell in mammalian liver Hydrophobic signals and control of transcription Action of hydrophobic signalling molecules Hormone Intracellular receptor protein Altered rate of protein synthesis (long-lasting effects) Altered rate of gene transcription Hydrophobic signalling molecules can bind to nuclear receptors to regulate gene transcription. Animation of regulation of transcription. Steroid hormones are hydrophobic signalling molecules. Animation of mechanism of steroid hormone action. The steroid hormone receptor proteins are transcription factors. Inhibitory protein complex Inactive transcription factor Hormone-binding site Steroid hormone Active transcription factor DNA-binding site exposed Thyroxine is a hydrophobic hormone that regulates the metabolic rate. Why is thyroxine not classified as a carbohydrate, lipid or protein? Thyroxine is released from the thyroid gland. Thyroxine absent Thyroid receptor protein bound to DNA Transcription of Na+/K+ ATPase gene inhibited Action of thyroxine Thyroxine Receptor protein undergoes conformational change 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+ ATP Transcription of Na+/K+ATPase gene Hydrophilic signals and transduction Hydrophilic ligands - Molecules that bind to sites on target proteins (receptors) at the surface of cells to trigger signal transduction. - Ligand binding triggers the receptor protein to undergo a conformational change. Hydrophilic signal Reception + transduction Amplification Second messenger Internal regulator Tissue-specific effectors Cell responses Action of hydrophilic signalling molecules Hormone (ligand) Receptor protein Signal transduction Cell responses (short-lasting effects) Peptide hormones are short chains of amino acids. • ADH • Insulin Neurotransmitters are chemical signals released from nerve endings that alter the activity of target cells. Axon Neurotransmitter substance Synapse Location of receptors Animation of action of acetylcholine. Hydrophilic signal transduction 2: receptors with kinase activity Part of receptor that binds insulin (alpha-subunit) Part of receptor with kinase activity (beta-subunit) Hydrophilic signal transduction 1: G-protein cascade Signal Adenylate cyclase enzyme Stimulatory Gprotein cAMP (second messenger) Animation of G-protein activation. Signal Inhibitory Gprotein Protein kinase A Membrane channels + pumps, microtubules, histones, specific enzymes 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 Animation of protein kinase activity triggered by adrenaline and tyrosine kinase activity. Insulin regulates the glucose concentration of the blood Beta-cells in pancreas release more insulin Insulin transported in blood ADH acts on adipose, liver and muscle cells Blood glucose concentration at set point More glucose is taken up by cells Blood glucose concentration falls Change detected Blood glucose concentration rises Action of insulin on fat and muscle cells GLUT4 Animation of insulin action. GLUT4 recruitment is also induced by exercise. Diabetes mellitus • A disease caused by defects in the insulin signalling system. • Two types of diabetes mellitus are recognised. • What are the general symptoms of diabetes mellitus? Cause Usual age of onset Nature of defect Treatment Type 1: Insulindependent diabetes Destruction of betacells in pancreas by immune system Childhood Type 2: Non-insulindependent diabetes Exact cause unknown Obesity is a risk factor Pancreas does not produce any insulin Target cells develop insulin resistance Loss of receptor function Eat less sugar and saturated fat Regular exercise Medication to lower blood glucose concentration Daily insulin injections and management of diet to control blood glucose concentration Adulthood Global prevalence of diabetes mellitus Numbers are millions! Review of diabetes mellitus - Animation of insulin production and type 1 diabetes mellitus. - Basic animation of type 2 diabetes mellitus. - Animation of type 2 diabetes mellitus. 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 ADH acts on kidney collecting ducts Change detected Blood water concentration rises Blood water concentration at set point More water reabsorbed into blood Less urine made Blood water concentration falls 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. Diabetes insipidus • Disease in which the water conservation mechanism of the kidneys fails. • What could the nature of the failure be? • What would the symptoms of diabetes insipidus be? 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 AQP2 ADH Phosphorylated target proteins Protein kinase A Symptoms of diabetes insipidus - Excessive thirst. - Production of large quantities of dilute urine (‘insipidus’ = lacks flavour). Overview of the action of ADH