1. Cell Communication Chapter 11 Biology Campbell Reece

2. Overview  We can look at simple organisms like yeast and bacteria as examples for all cells Ex. Yeast communicate to identify their mateEx. Yeast communicate to identify their mate  Signal-transduction pathway - The process by which a signal on a cell’s surface is converted into a specific cellular response

3. Communication Between Yeast

4. Direct Contact  Direct contact – through cell junctions that directly connect the cytoplasm of one cell to the cytoplasm of an adjacent cell  Or through receptors on the surface of cells

5. Local vs. Long Distance Signaling  Local – cells secrete a local regulator, a substance that influences cells in the vicinity  Greater distances – cells secrete hormones which can travel far

6. 3 stages of cell signaling 1. Reception – the target cell’s detection of a signal coming from outside the cell 2. Transduction – converts the signal to a form that can bring about a specific cellular response  Sometimes occurs as a single step  Sometimes requires a series of different molecules – signal- transduction pathway

7. 3 stages of cell signaling 3. Response – may be almost any imaginable cellular activity  Ex. Enzyme catalysis, rearrangement of the cytoskeleton, activation of specific genes

8. Signal Receptors  A signal molecule binds to a receptor protein in the cell membrane (ligand binding), causing the protein to change shape Ligand – a small molecule that specifically binds to a larger oneLigand – a small molecule that specifically binds to a larger one  The change of shape may directly activate the receptor or may cause the aggregation of two or more receptor molecules

9. G-Protein-Coupled Receptors  A plasma membrane receptor that works with the help of a G protein  G proteins are important in embryonic development, sensory reception (visual & smell)  G protein functions as an on/off switch When GDP (guanosine diphosphate) is attached the G protein is inactiveWhen GDP (guanosine diphosphate) is attached the G protein is inactive When GTP (guanosine triphosphate) is attached the G protein is activeWhen GTP (guanosine triphosphate) is attached the G protein is active

10. Example G-Protein Receptor 1. A signal molecule binds to the G- protein-linked receptor 2. The receptor changes shape & binds to an inactive G protein 3. A GTP displaces the GDP, activating the G protein 4. G protein binds to another protein, usually an enzyme, & alters its activity, triggering the next step

11. G Protein-Coupled Receptors

12. Receptor Tyrosine Kinases  A kinase is an enzyme that catalyzes the transfer of phosphate groups  Specialized for triggering more than one signal-transduction pathway at once  Before a signal molecule binds, the receptors exist as individual polypeptides

13. Activation of Tyrosine-Kinase 1. The ligand binding causes two receptor polypeptides to aggregate, forming a dimer (a protein with two polypeptides) 2. This activates the tyrosine-kinase, which then adds phosphates to the tyrosines on the tail 3. It is now recognized by specific relay proteins inside the cell

14. Activation of Tyrosine-Kinase 4. Each protein binds to a specific phosphorylated tyrosine, and changes shape 5. One tyrosine-kinase receptor dimer may activate ten or more different proteins simultaneously 6. Triggering as many different transduction pathways & cellular responses

15. Receptor Tyrosine Kinases

16. Ion-Channel Receptors  Ligand-gated ion channels – protein pores that open or close in response to a chemical signal, allowing or blocking the flow of specific ions  Very important in the nervous system

17. Intracellular Receptors  Not all signal receptors are membrane proteins  Some are proteins in the cytosol or nucleus of target cells  To reach these receptors, the chemical messenger must be able to pass through the membrane Steroid hormones, nitric oxideSteroid hormones, nitric oxide

18. Intracellular Receptors

19. Signal-Transduction Pathways  When signal receptors are membrane proteins, the transduction stage is usually a multistep pathway  This allows the signal to be greatly amplified  Relay molecules, usually proteins, relay the signal from receptor to response

20. Protein Phosphorylation  The activation of a protein by adding one or more phosphate groups to it  Protein kinase – an enzyme that transfers phosphate groups from ATP to a protein  Many pathways contain protein kinases that create a “phosphorylation cascade”  Protein phosphatases – enzymes that remove phosphate groups from proteins

21. Protein Phosphorylation

22. Second Messengers  Not all components of signal- transduction pathways are proteins  Second messengers - Small, nonprotein, water-soluble molecules or ions Can readily spread throughout a cell by diffusionCan readily spread throughout a cell by diffusion Two most widely used are cyclic AMP and calcium ionsTwo most widely used are cyclic AMP and calcium ions

23. Cyclic AMP  The use of cyclic AMP as a second messenger was discovered by Earl Sutherland  He found that when epinephrine binds to the plasma membrane of a liver cell, the concentration of cAMP in the cytosol increased Adenylyl cyclase converts ATP to cAMP in response to the epinephrineAdenylyl cyclase converts ATP to cAMP in response to the epinephrine

24. cAMP as a Second Messenger

25. Calcium Ions  Neurotransmitters, growth factors, and some hormones induce responses that increase Ca 2+ concentration  More widely used as a second messenger than cAMP  Causes many responses including muscle contraction, cell division and secretion of certain substances

26. DAG and IP 3  Diacylglycerol (DAG) and inositol triphosphate (IP 3 ) are other second messengers used to release calcium from cell’s endoplasmic reticulum  Calcium ions may activate a signal- transduction protein directly or by means of calmodulin Calmodulin – a Ca 2+ binding proteinCalmodulin – a Ca 2+ binding protein

27. Calcium in signaling pathways

28. Cellular Responses  In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus An ion channel in the plasma membrane may open or closeAn ion channel in the plasma membrane may open or close Cell metabolism may changeCell metabolism may change Synthesis of proteins may be regulated by turning on or off the genesSynthesis of proteins may be regulated by turning on or off the genes

29. Cellular Responses

30. Signal Amplification  Elaborate enzyme cascades amplify the cell’s response to a signal  At each step, the number of activated molecules is much greater than the preceding step

31. The Specificity of Cell Signaling  Both the liver and heart respond to epinephrine, but in different ways  Different kinds of cells have different collections of proteins

32. Branching and “Cross-talk”  Branching of pathways and “cross- talk” (interaction) between pathways are important in regulating and coordinating the cellular response  The use of some of the same proteins in more than one pathway allows the cell to economize on the number of different proteins it must make

33. Scaffolding Proteins  Proteins are too large to diffuse quickly through the cytosol  Scaffolding proteins – large relay proteins to which several other relay proteins are simultaneously attached Enhances the speed and accuracy of signal transferEnhances the speed and accuracy of signal transfer

34. Turning “Off” the Signal  The signal molecule leaves the receptor… The GTP bound to the G protein is hydrolyzed to GDPThe GTP bound to the G protein is hydrolyzed to GDP Phosphodiesterase converts cAMP to AMPPhosphodiesterase converts cAMP to AMP Protein phosphatases inactivate phosphorylated kinasesProtein phosphatases inactivate phosphorylated kinases  The cell is now ready to respond to a fresh signal