1. Chapter 15 Baboon text Cell Signaling and Communication 15.1 What Are Signals, and How Do Cells Respond to Them? Cells receive signals from 1. Physical environment Ex: light, temperature, touch, sound and chemicals 2. Other cells- primarily in the form of chemicals and touch.

2. 15.1 What Are Signals, and How Do Cells Respond to Them? Autocrine signals affect the cells that made them. Paracrine signals affect nearby cells. Hormones travel to distant cells, usually via the circulatory system.

3. Local Diffusion e.g., Histamine released from damaged cells in inflammation e.g., Interferon release by viral-infected cells

4. Receptor proteins have very specific binding sites for chemical signal molecules, or ligands. Binding the ligand causes receptor protein to change shape. The binding is reversible. LIGANDS

5. Ligands can bind to –Cytoplasmic receptor- located in the cytoplasm or nucleus. Ligand must be small and non-polar (lipid soluble) Cytoplasmic- causes change in protein regulation –Ex: glycogen breakdown Nuclear- stimulates or inhibits transcription –Membrane receptor- located within the membrane. Ligand is large and/or polar (water soluble) Leads to stimulation or inhibition of transcription; either stopping, starting, increasing or decreasing production of particular activity

6. e.g., nitric oxide and steroid hormone Intracellular Reception Extracellular Reception Ligands e.g., insulin and epinephrine

7. Examples of Surface Receptors

8. Three Stages of Signal Transduction 1.Reception of extracellular signal by cell 2.Transduction of signal from outside of cell to inside of cell—often multi-stepped Note not necessarily transduction of ligand 3.Cellular Response Response is inititiated and/or occurs entirely within receiving cell

9. Three Stages of Signal Transduction

10. Three Stages 2a. Transduction 2b. Transduction 1. Reception 3. Response

11. Three Stages 2a. Transduction 2b. Transduction 2c. Transduction 2d. Transduction 1. Reception 3. Response Responses usually involve increasing or decreasing some Protein’s Function

12. Various Responses Note that more than one response can result from the reception of a single ligand

13. A signal transduction pathway: The signal causes receptor protein to change conformation. Conformation change gives it protein kinase activity. Phosphorylation alters function of a responder protein. Various Responses

16. 15.2 How Do Signal Receptors Initiate a Cellular Response? Types of plasma membrane receptors: Ion channels Protein kinases (Tyrosine-kinase receptors) G protein-linked receptors

17. 15.2 How Do Signal Receptors Initiate a Cellular Response? Ion channel receptors: channel proteins that allow ions to enter or leave a cell. Example: acetylcholine binds which allows Na+ into cell. This causes a muscle to contract Ion-Channel Receptors

18. Figure 15.5 A Gated Ion Channel Ion-Channel Receptors

20. 15.2 How Do Signal Receptors Initiate a Cellular Response? G protein-linked receptors: the seven-transmembrane-spanning G protein-linked receptors. G proteins: mobile membrane proteins with three subunits. G Protein-Linked Receptors

21. 15.2 How Do Signal Receptors Initiate a Cellular Response? Signal outside cell activates G protein linked receptor which activates G protein inside cell. This then activates the protein and it moves through plasma membrane until it encounters an effector protein. Binding activates the effector which causes a change in cell function (activation/inhibition). G Protein-Linked Receptors

22. Figure 15.7 A G Protein-Linked Receptor (Part 1) G Protein-Linked Receptors Effector protein can cause amplification

23. G Protein-Linked Receptors the more ligand binding, the more K + in cytoplasm note how activation is reversible

24. 15.3 How Is a Response to a Signal Transduced through the Cell? Protein kinase receptors—catalyze the transfer phosphate from ATP to a target protein causing conformation and activity. Ex: Insulin (ligand) binds to receptor which phosphorylates and activates glucose transporters. Protein Kinase & Phosphatase

25. Figure 15.10 A Protein Kinase Cascade Protein Kinase & Phosphatase

26. Signal Amplification (Direct Cascade) 15.3 How Is a Response to a Signal Transduced through the Cell? Direct transduction- the receptor causes the change and occurs at membrane.

27. Signal Amplification (Indirect Cascade) 15.3 How Is a Response to a Signal Transduced through the Cell? Indirect transduction- involves a second messenger.

28. 15.3 How Is a Response to a Signal Transduced through the Cell? Second messengers were discovered in research on the liver enzyme glycogen phosphorylase, and how it is activated by epinephrine. (Read up on Sutherland’s investigations with epinephrine p. 340-41) Binding of the hormone to the membrane receptor caused production of a small molecule (cyclic AMP, or cAMP) that diffused into the cytoplasm to activate the enzyme.

29. 15.3 How Is a Response to a Signal Transduced through the Cell? The signal is the first messenger. The second messenger is released into the cytoplasm after signal binds to receptor. Second messengers affect many processes in the cell. Also amplify the signal—one epinephrine molecule leads to production of many cAMP.

30. Second Messengers

31. Specificity of Cell Signaling 1.Note how same ligand gives rise to different responses 2.Cells differ in terms of their proteins 3.Different proteins respond differently to the same environmental signals 4.(note, though, same receptors, different relay) 5.Different cells behave differently because some, but not all proteins can differ between cell types

32. Chemical Signaling Between Cells

33. 15.4 How Do Cells Change in Response to Signals? In your trifold book add the following information: Include details on the front and examples for each on the back. ReceptionTransductionResponse Ion channels G-Protein Linked Protein Kinase

34. Acknowledgements biology.ucf.edu/courses/bsc2010/08-2010C-02.PPT www.aw.com/bc/ppt/marieb_ap/chap03c.ppt http://zeus.uwindsor.ca/courses/biology/zielinski/204/comm1.ppt http://vaccine.chonbuk.ac.kr/images/cell/Chapter%2015%20Cell.ppt http://faculty.uca.edu/~jmurray/BIOL1440/lec/lec15.ppt \http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/7-signal.ppt http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/9-glycogen.ppt http://homepage.smc.edu/chen_thomas/Bio21/Chpt%2011%20Cell%20Comm.ppt

35. Putting the information to work

36. Cell Cycle Control System How is the cell cycle controlled Restriction Checkpoints- sites where cell division are either prevented or stopped Locations –G1- commits the cell to division –G2 –M –Ex: At the G1 checkpoint, if the cycle is stopped, cell will enter G0

37. Checkpoints are controlled by protein activity –2 main proteins Cyclins- proteins continually produced in cells Kinase-proteins that activate or inactivate target proteins by phosphorylating them –Phosphorylation: breaking down ATP and adding a phosphate group »This changes the shape of the target protein Target proteins –directly regulate the cell cycle Cell Cycle Control System

38. Ex: G1 checkpoint Proteins involved –Cyclin –Cyclin dependent kinase (Cdk) –Rb (target protein) normally inhibits the cell cycle at G1 checkpoint How it works When Cdk binds with a cyclin, it becomes activated Cdk/cyclin complex phosphorylates RB Rb becomes inactive and can no longer inhibit the cell cycle Cell proceeds to stage Synthesis NOTE: RB and other target proteins in the cell cycle control system act as tumor suppressors by stopping uncontrolled cell division. LOOK AT FIGURE 9.6 IN YOUR BABOON TEXT Cell Cycle Control System

39. LOOK AT FIGURE 9.6 IN YOUR BABOON TEXT