VEA Bringing Learning to Life Program Support Notes Senior Secondary 26mins Cellular Signalling Teacher Notes by Sue Wright, B. Sc., Dip. Ed. Produced by VEA Pty Ltd Commissioning Editor Christine Henderson B.Sc. Ph.D. Dip.Ed. Executive Producer Mark McAuliffe Dip.Art (Film & TV) Dip.Ed. B.Ed. Ph.D. © VEA Pty. Ltd. Suitable for: Biology To order or inquire please contact VEA: Australia 111A, Mitchell Street, Bendigo, Victoria 3550 FREECALL: 1800 034 282 Phone: (03) 5442 2433 Facsimile: (03) 5441 1148 New Zealand PO BOX 4390, Shortland St., Auckland FREECALL: 0800 486 688 Facsimile: 0800 488 668 WARNING E-mail vea@vea.com.au Website www.vea.com.au The Copyright proprietor has licensed the motion picture contained on this video cassette for non-theatrical use only and prohibits any other use, copying, reproduction or performance in public, in whole or part. The penalties for unauthorised copying of this program include a $50,000 fine for individuals and a $250,000 fine for institutions. These notes can be freely copied for classroom use only. Cellular Signalling For Teachers: Brief Summary of Program That certain cells produce certain substances under certain conditions is well known to Biology students. What occurs inside the cell to translate a signal into a response is less often examined but of growing importance to Biologists. This program explores the need for cellular signals, the nature of the signals, how signals are transported to the cell and how different signals reach their extracellular and intracellular receptors. It also examines what happens after the cell processes the signals by discussing G-proteins, second messengers, activation of proteins and signalling cascades. Signal divergence and convergence are also examined. The program uses graphics extensively to explain these complex processes and many examples that will be familiar to senior secondary and early tertiary students. DVD Timeline 00:00:00 00:04:16 00:04:51 00:08:06 00:08:24 00:14:27 00:14:59 00:20:06 00:20:40 00:23:56 00:24:20 00:25:07 00:25:36 Introducing Cellular Signalling Summary Types of Signalling Part 1 Summary Types of Signalling Part 2 Summary Signal Processing Summary Signal Amplification Summary Conclusion Credits Program end Other Relevant Programs Available from VEA Macromolecules 1 – Carbohydrates, Lipids & Nucleic Acids Macromolecules 2 - Proteins & Proteomics Cellular Signalling Cell City Series Acids and Bases Bonding Between Molecules – Chemical Bonding Series Please visit our website for many more relevant programs www.vea.com.au VEA – Bringing Learning to Life 2 Cellular Signalling For Students: Before Viewing the Program 1. What kinds of messages would a unicellular organism need to receive and process in order to survive? What about the cells of a multicellular organism? What signals and processing is required? 2. What can you recall about the structure of the cell membrane? You could find this out by passing a marker from one student to the next and having each student add to a diagram with a structure or annotation. Consider what the chemical composition of the cell membrane is and the role of the elements of the membrane. 3. Define an enzyme. How do they work? Why is an enzyme specific to a substrate? 4. What is the role of hormones? How are hormones transported from the cell that secretes them to the cell that reacts to them? Are all hormones endocrine hormones? If not what other kinds of hormones are there? 3 Cellular Signalling While Viewing the Program 1. What had to evolve before multicellular existence could succeed? _______________________________________________________________________________ _______________________________________________________________________________ 2. What do unicellular organisms need to coordinate? What about cells in simple multicellular organisms? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 3. List the types of signal molecules. _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 4. What does successful signalling involve? _______________________________________________________________________________ _______________________________________________________________________________ 5. List the traditional biological receptors. How has the definition of a receptor been modified? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 6. Define signal transduction. _______________________________________________________________________________ _______________________________________________________________________________ 7. What kinds of signalling molecules can pass directly across the cell membrane? _______________________________________________________________________________ 8. Why are carrier proteins necessary to carry some signals? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 4 Cellular Signalling 9. What is paracrine signalling? How long do the signalling molecules last? What happens to them? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 10. What rapid signalling system has evolved to rapidly cover the long distances in large animals? How does it work? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 11. What is endocrine signalling? How does its speed compare with that of synaptic signalling? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 12. What is autocrine signalling? What is its function? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 13. How do gap junctions work? What is an example of a situation where they are involved? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 5 Cellular Signalling 14. What happens to a cell deprived of all signals? How do you think this would be carried out? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 15. What two characteristics does a signalling molecule have to have to pass directly through a cell membrane? What is an example of such a molecule? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 16. What are the effects of nitric oxide signals? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 17. List the steroid hormones? How do they signal a cell? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 18. What are steroid hormones synthesised from? ______________________________________________________________________________ 19. Sometimes the steroid/ receptor complex causes the production of a protein which in turn causes the production of another protein. What is this kind of response called? _______________________________________________________________________________ 6 Cellular Signalling 20. Not all cells will have the same response to a steroid hormone. Give an example of this from the program. Can you think of a further example? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 21. What is a signalling molecule released in response to prolonged low blood glucose? Where are its target cells? What protein would these target cells produce in response to the signal? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 22. In what two ways does vitamin D act to increase calcium levels in the body? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 23. How do thyroid hormones which are insoluble in water, travel in the watery blood plasma? _______________________________________________________________________________ 24. Water soluble hormones can travel easily in the blood plasma but can’t cross the lipid bilayer that makes up the cell membrane. How is this difficulty overcome? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 7 Cellular Signalling 25. Complete the following table Signal Lifetime Local mediators and neurotransmitters Water soluble hormones Steroids Thyroid hormones 26. What opens a ligand gated channel? What opens a voltage gated channel? _______________________________________________________________________________ _______________________________________________________________________________ 27. What are three events that are regulated by ion channels? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 28. Where would you find a G-protein? What would it be coupled to? What concentrations can it change? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 29. Why are Calcium ions and cAMP called second messengers? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 8 Cellular Signalling 30. What are two examples of changes to proteins caused by phosphorylation? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 31. Calcium is an important second messenger in cells. Where is it mobilised from when it is required? How does it get into the cytosol? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 32. How does calcium act directly to activate enzymes? What about indirectly? Where does it go when it is no longer required? _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 33. Complete the following table: Molecule or structure Number involved in signalling cascade Rhodopsin molecules Transducin molecules Phosphodiesterase molecules cAMP molecules Sodium channels Sodium ions 9 Cellular Signalling 34. What are the 2 hormones that target liver cells whose signals converge? _______________________________________________________________________________ _______________________________________________________________________________ 35. List the divergent responses of the neutrophil to the specific breakdown products of bacteria and suggest why each one would be necessary. _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ _______________________________________________________________________________ 10 Cellular Signalling After Viewing the Program 1. Find out some more about programmed cell death. Where does it start? Why is it called programmed? What is its role in the development of an embryo? 2. What happens when the body has insufficient vitamin D? What happens when there is too much? 3. Find out some more about the role of ion channels in the transmission of nerve impulses and in the opening and closing of stomata. 4. There is much in the media about the use of anabolic steroids. What are they? Who uses them? Why are they harmful? 5. Cellular signals are very important in the immune system. How does the body recognise self and non-self? What happens when transplanted tissue is rejected? When there is an allergic reaction? When there is an autoimmune disease? 6. Adding phosphate to a protein is often how the activity of the protein is altered. Find out some more about this. 11 Cellular Signalling Suggested Student Responses 1. What had to evolve before multicellular existence could succeed? A signalling mechanism so that each cell knew its role 2. What do unicellular organisms need to coordinate? What about cells in simple multicellular organisms? Aggregation for feeding and reproduction. Each cell needs to differentiate and divide in synchrony with other cells of the organism for multicellular existence to succeed 3. List the types of signal molecules. Proteins, small peptides, amino acids, nucleotides, steroids, retinoids, fatty acid derivatives, nitric oxide and carbon monoxide. 4. What does successful signalling involve? A sender, information being sent or a signal and a receiver or receptor. 5. List the traditional biological receptors. How has the definition of a receptor been modified? Photo, thermo, mechano and chemo receptors. The modified definition includes a molecule that receives an extracellular message. 6. Define signal transduction. A process by which a cell converts an extracellular signal into a response. 7. What kinds of signalling molecules can pass directly across the cell membrane? Lipids or lipid soluble substances. 8. Why are carrier proteins necessary to carry some signals? Because many signals are insoluble in the watery blood plasma and tissue fluid so they need to be carried to their target cell. 9. What is paracrine signalling? How long do the signalling molecules last? What happens to them? Short lived signals that are only taken up by neighbouring target cells. They only last a short time after which they are destroyed by enzymes or immobilised. 10. What rapid signalling system has evolved to rapidly cover the long distances in large animals? How does it work? Synaptic signalling. Neurons allow electrical impulses to travel along axons. When this impulse reaches the terminals at the end of the axon a chemical called a neurotransmitter is released in the synapse and is picked up by a post-synaptic receptor 11. What is endocrine signalling? How does its speed compare with that of synaptic signalling? Endocrine signals are molecules called hormones which are released into the blood stream of an animal, or the sap of a plant, and are carried to the target cell. This is much slower than synaptic signalling as it can only be as fast as sap or blood flow. 12. What is autocrine signalling? What is its function? Autocrine signalling occurs when cells secrete signalling molecules that bind back to its own receptors. Groups of identical cells use this type of signalling so that groups of identical cells develop together. 13. How do gap junctions work? What is an example of a situation where they are involved? Gap junctions are specialised cell-to-cell junctions that can form between closely opposed plasma membranes directly connecting cytoplasm through water filled channels. Small signalling molecules and ions called intracellular mediators, such as calcium ions and cyclic AMP can pass through them, but macromolecules can’t do so. Studies of embryos with water-soluble dyes show that embryo cells make and break these connections in interesting patterns probably to coordinate the behaviour of cells. 12 Cellular Signalling 14. What happens to a cell deprived of all signals? How do you think this would be carried out? These cells will activate a suicide program called programmed cell death. A programmed series of enzyme activations would be responsible for this. 15. What two characteristics does a signalling molecule have to have to pass directly through a cell membrane? What is an example of such a molecule? The molecule needs to be small and hydrophobic. Nitric oxide is an example of such a molecule. 16. What are the effects of nitric oxide signals? It signals smooth muscle cells to relax and has long been used to treat angina which is heart pain caused by not enough blood flow to heart muscle. Nitric oxide also activates macrophages and neutrophils to kill invading micro-organisms. 17. List the steroid hormones? How do they signal a cell? Steroid hormones include cortisol, the steroid sex hormones and vitamin D in vertebrates and the moulting hormone in insects. They are able to pass through the plasma membrane by diffusion and bind with an intracellular receptor. The receptor/ hormone complex can pass through a nuclear pore into the nucleus where it interacts with DNA directly to alter the rate of synthesis of a particular protein. 18. What are steroid hormones synthesized from? Cholesterol 19. Sometimes the steroid/ receptor complex causes the production of a protein which in turn causes the production of another protein. What is this kind of response called? A delayed secondary response. 20. Not all cells will have the same response to a steroid hormone. Give an example of this from the program. Can you think of a further example? The steroid hormone testosterone causes the development of facial hair and also deepening of the voice. There are many other examples such as oestrogen and secondary sexual characteristics in females. 21. What is a signalling molecule released in response to prolonged low blood glucose? Where are its target cells? What protein would these target cells produce in response to the signal? The molecule is cortisol and its target cells are in the liver. The liver would produce glucagon in response to this signal. 22. In what two ways does vitamin D act to increase calcium levels in the body? It stimulates reabsorption of calcium in the kidneys and increases uptake of calcium in the gut. 23. How do thyroid hormones which are insoluble in water, travel in the watery blood plasma? They are carried by a carrier protein. 24. Water soluble hormones can travel easily in the blood plasma but can’t cross the lipid bilayer that makes up the cell membrane. How is this difficulty overcome? Water-soluble signalling molecules can’t pass through the cell membrane so they must be detected by receptors on the cell surface. Their receptors, which are proteins, are found embedded in the plasma membrane 25. Complete the following table Signal Local mediators and neurotransmitters Water soluble hormones Steroids Thyroid hormones Lifetime Less than a second Minutes Hours Days 13 Cellular Signalling 26. What opens a ligand gated channel? What opens a voltage gated channel? A water soluble signalling molecule called a ligand. A change in membrane potential. 27. What are three events that are regulated by ion channels? They are responsible for the excitation of muscle cells, are involved in mediating the electrical signalling of nerve cells, are responsible for the leaf closing of Mimosa plants, allow single celled Paramecium to reverse after a collision as well as being involved in regulating stomatal aperture. 28. Where would you find a G-protein? What would it be coupled to? What concentrations can it change? G proteins are found coupled to receptors that have 7 transmembrane domains. It regulates activity in the cell usually by changing the concentration of second messengers such as cyclic AMP (cAMP) or calcium ions. 29. Why are Calcium ions and cAMP called second messengers? The first messenger would be the G-protein and this effects the concentration of cAMP or calcium ions so they are called second messengers. 30. What are two examples of changes to proteins caused by phosphorylation? Phosphorylation of a channel protein can cause the channel to open. Phosphorylation of an enzyme can activate it by opening its active site to allow substrate binding to occur... 31. Calcium is an important second messenger in cells. Where is it mobilised from when it is required? How does it get into the cytosol? Calcium is stored in E.R. and mitochondria. It can also come from outside the cell. Calcium channels are opened to release intracellular and/ or extracellular Calcium when it is required as a second messenger. 32. How does calcium act directly to activate enzymes? What about indirectly? Where does it go when it is no longer required? The concentration of calcium in the cell can directly regulate the activity of enzymes such as protein kinases. Indirectly it can form a complex with an intra cellular Calcium receptor called Calmodulin. The calcium/ calmodulin receptor activates different kinases. The calcium can be rapidly removed from the cytosol back to membrane bound storage areas. 33. Complete the following table Molecule or structure Rhodopsin molecules Transducin molecules Phosphodiesterase molecules cAMP molecules Sodium channels Sodium ions Number involved in signalling cascade 1 500 500 100 000 250 1-10 million 34. What are the two hormones that target liver cells whose signals converge? Adrenaline and glucagon. 35. List the divergent responses of the neutrophil to the specific breakdown products of bacteria and suggest why each one would be necessary. Changes in cell adhesion so cell can adhere to bacterial cells or toxins. Changes in cell shape so that bacterial cells or toxins can be engulfed then broken down. Changes in cell motility so that neutrophil can move where it is needed. Increased oxygen uptake to allow for increased cellular respiration. Release of hydrogen peroxide produced by increased cellular metabolism. Release of proteases to breakdown bacterial protein. 14