1. AH Biology: Unit 1 Communication Within Multicellular Organisms

2. Communication within multicellular organisms -General principles. -Hydrophobic signals and control of transcription. -Hydrophilic signals and transduction.

3. In animals communication is mediated by nervous transmission and hormonal secretion.

4. Nervous communication Hormonal communication Nature of signalElectrical impulses and extracellular signalling molecules Extracellular signalling molecules Transmission of signal Along the axons of neurons Through the bloodstream Target cellsAny cells with connections to neurons (effectors) Almost any cells in the body Time for response to occur FasterSlower Duration of response TransientLonger lasting Extent of responseLocalisedWidespread

5. Coordination is important for homeostasis

6. Coordination allows integrated homeostatic responses to be made. Monitoring centres Controlled system Error- correcting mechanisms Set point values Disturbances Error signal Coordinated responses

7. Coordination of responses allows animals to cope with physiological stress, eg a human doing exercise...

8. Exercise Cardiovascular challenge Ventilatory challenge Metabolic challenge Thermoregulatory challenge Osmoregulatory challenge

9. 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)

10. 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)

11. Different cell types produce specific signalling molecules.

12. Spatial organisation of signalling molecules Hormones Neurotransmitters Animal pheromones Eukaryotic cell: 50 μ m Distance: 1 nm 1 μ m 1 mm 1 m 1 km

13. How does a target cell ‘know’ that it should respond to a specific signal?

14. Cells can only detect and respond to signals if they possess a specific receptor. Insulin Adrenaline Insulin receptor protein Adrenaline receptor protein

15. Different cell types may show a specific tissue response to the same signal. Beta- receptor AdrenalineBeta- receptor Adrenaline Cell in mammalian salivary gland Cell in mammalian liver Amylase release stimulatedGlycogen breakdown stimulated

16. Hydrophobic signals and control of transcription

17. Action of hydrophobic signalling molecules Altered rate of gene transcription Altered rate of protein synthesis (long-lasting effects) Intracellular receptor protein Hormone

18. Hydrophobic signalling molecules can bind to nuclear receptors to regulate gene transcription. AnimationAnimation of regulation of transcription.

19. Steroid hormones are hydrophobic signalling molecules. AnimationAnimation of mechanism of steroid hormone action.

20. The steroid hormone receptor proteins are transcription factors. Hormone-binding site DNA-binding site exposed Inhibitory protein complex Inactive transcription factor Active transcription factor Steroid hormone

21. Thyroxine is a hydrophobic hormone that regulates the metabolic rate. Why is thyroxine not classified as a carbohydrate, lipid or protein?

22. Thyroxine is released from the thyroid gland.

23. Thyroxine absent Transcription of Na + /K + ATPase gene inhibited Thyroid receptor protein bound to DNA

24. Action of thyroxine Transcription of Na + /K + ATPase gene Synthesis of Na + /K + ATPase Receptor protein undergoes conformational change Thyroxine

25. Transcription of Na + /K + ATPase gene Synthesis of Na + /K + ATPase More Na + /K + ATPases in cell membrane Increased metabolic rate ATP degraded faster Insertion into membrane

26. Hydrophilic signals and transduction

27. 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.conformational change

28. Hydrophilic signal Reception + transduction Amplification Second messenger Internal regulator Tissue-specific effectors Cell responses

29. Action of hydrophilic signalling molecules Receptor protein Hormone (ligand) Signal transduction Cell responses (short-lasting effects)

30. Peptide hormones are short chains of amino acids. ADH Insulin

31. Neurotransmitters are chemical signals released from nerve endings that alter the activity of target cells. AnimationAnimation of action of acetylcholine. Location of receptors Axon Synapse Neurotransmitter substance

32. Hydrophilic signal transduction 2: receptors with kinase activity Part of receptor that binds insulin (alpha-subunit) Part of receptor with kinase activity (beta-subunit)

33. Hydrophilic signal transduction 1: G-protein cascade AnimationAnimation of G-protein activation. Signal Stimulatory G- protein Inhibitory G- protein Adenylate cyclase enzyme cAMP (second messenger) Protein kinase A Membrane channels + pumps, microtubules, histones, specific enzymes

34. Animation of protein kinase activity triggered by adrenaline and tyrosine kinase activity.protein kinase tyrosine kinase 2. Kinase enzyme phosphorylates itself (autophosphorylation) 1. Insulin binds to receptor P P P P P 3. Receptor phosphorylates insulin receptor substrate (IRS-1) 4. Phosphorylated IRS-1 acts on effectors to trigger cell responses

35. 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 More glucose is taken up by cells Blood glucose concentration falls Blood glucose concentration at set point Blood glucose concentration rises Change detected

36. Action of insulin on fat and muscle cells AnimationAnimation of insulin action. GLUT4

37. GLUT4 recruitment is also induced by exercise.

38. 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?

39. Type 1: Insulin- dependent diabetes Type 2: Non-insulin- dependent diabetes CauseDestruction of beta- cells in pancreas by immune system Exact cause unknown Obesity is a risk factor Usual age of onset ChildhoodAdulthood Nature of defect Pancreas does not produce any insulin Target cells develop insulin resistance Loss of receptor function TreatmentDaily insulin injections and management of diet to control blood glucose concentration Eat less sugar and saturated fat Regular exercise Medication to lower blood glucose concentration

40. Global prevalence of diabetes mellitus Numbers are millions!

41. Review of diabetes mellitus -Animation of insulin production and type 1 diabetes mellitus.Animation -Basic animation of type 2 diabetes mellitus.animation -Animation of type 2 diabetes mellitus.Animation

42. Terrestrial vertebrates require mechanisms for conserving water Thank goodness I can make ADH!

43. ADH regulates the body’s water balance Pituitary gland releases more ADH ADH transported in blood ADH acts on kidney collecting ducts More water reabsorbed into blood Less urine made Blood water concentration falls Blood water concentration at set point Blood water concentration rises Change detected

45. Mechanism of action of ADH Lumen of collecting duct BloodCollecting duct cell 1. ADH 2. ADH receptor 3. Activation of protein kinase A 5. Fusion of vesicles containing AQP2 water channel proteins H2OH2O 4. Protein phosphorylation

46. Aquaporins are protein channels that allow efficient transmembrane movement of water. AnimationAnimation of water movement through an aquaporin channel.

47. 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?

48. 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.

49. Possible causes of diabetes insipidus Lumen of collecting duct BloodCollecting duct cell ADH ADH receptor Protein kinase A AQP2 Phosphorylated target proteins

50. Symptoms of diabetes insipidus -Excessive thirst. -Production of large quantities of dilute urine (‘insipidus’ = lacks flavour).

51. OverviewOverview of the action of ADH