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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.
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AH Biology: Unit 1Communication 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.
Coordination allows integrated homeostatic responses to be made. Disturbances Coordinated responses Error- correcting mechanisms Controlled system Monitoring centres Error signal Set point values
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)
Spatial organisation of signalling molecules Eukaryotic cell: 50 μm Distance: 1 nm 1 μm 1 mm 1 m 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. Insulin Adrenaline Insulin receptor protein Adrenaline receptor protein
Different cell types may show a specific tissue response to the same signal. Beta-receptor Beta-receptor Adrenaline Adrenaline Amylase release stimulated Glycogen breakdown stimulated Cell in mammalian salivary gland Cell in mammalian liver
Action of hydrophobic signalling molecules Hormone Altered rate of protein synthesis (long-lasting effects) Intracellular receptor protein 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 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 ATP degraded faster Increased metabolic rate Insertion into membrane Synthesis of Na+/K+ ATPase Transcription of Na+/K+ATPase gene
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. Animation of action of acetylcholine. Axon Neurotransmitter substance Synapse Location of receptors
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 Signal Animation of G-protein activation. Adenylate cyclase enzyme - + Stimulatory G-protein Inhibitory G-protein + Membrane channels + pumps, microtubules, histones, specific enzymes + cAMP (second messenger) Protein kinase A
1. Insulin binds to receptor Animation of protein kinase activity triggered by adrenaline and tyrosine kinase activity. 2. Kinase enzyme phosphorylates itself (autophosphorylation) 4. Phosphorylated IRS-1 acts on effectors to trigger cell responses P P P P P 3. Receptor phosphorylates insulin receptor substrate (IRS-1)
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 Change detected More glucose is taken up by cells Blood glucose concentration falls Blood glucose concentration rises Blood glucose concentration at set point
Action of insulin on fat and muscle cells GLUT4 Animation of insulin action.
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?
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 More water reabsorbed into blood Less urine made Blood water concentration falls Blood water concentration rises Blood water concentration at set point
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).