Warm-Up

1. Warm-Up • Why do you communicate? • How do you communicate? • How do you think cells communicate? • Do you think bacteria can communicate? Explain.

2. Warm-Up • Compare the structure & function of these receptor proteins: GPCR, tyrosine kinase and ligand-gated ion channels. • What is a second messenger? What are some examples of these molecules? • What are the possible responses to signal transduction in a cell?

3. Cell Communication CHAPTER 11

4. Figure 11.1

5. Figure 11.1a Epinephrine

6. Evolution of Cell Signaling • The yeast, Saccharomyces cerevisiae, has two mating types, a and  • Cells of different mating types locate each other via secreted factors specific to each type • Signal transduction pathways convert signals received at a cell’s surface into cellular responses • The molecular details of signal transduction in yeast and mammals are strikingly similar

7. αfactor Receptor Exchangeof matingfactors 1 a α Figure 11.2-1 Yeast cell,mating type a Yeast cell,mating type α a factor

8. αfactor Receptor Exchangeof matingfactors 1 2 a α Figure 11.2-2 Yeast cell,mating type a Yeast cell,mating type α a factor Mating a α

9. αfactor Receptor Exchangeof matingfactors 3 2 1 a α Figure 11.2-3 Yeast cell,mating type a Yeast cell,mating type α a factor Mating a α New a/ cell a/ α

10. Pathway similarities suggest that ancestral signaling molecules that evolved in prokaryotes and single-celled eukaryotes were adopted for use in their multicellular descendants • Cell signaling is critical in the microbial world • A concentration of signaling molecules allows bacteria to sense local population density in a process called quorum sensing

11. Do bacteria communicate? Bonnie Bassler on How Bacteria “Talk”

12. Video Questions: • Why are scientists studying how bacteria (and not just human cells) communicate? • What is quorum sensing? • Describe how Vibrio fischeri use quorum sensing in squid. • According to Bonnie Bassler (Princeton University), what are scientists hoping to use as the next class of antibiotics?

13. Cell Signaling Animal cells communicate by: • Direct contact (gap junctions) • Secreting local regulators (growth factors, neurotransmitters) • Long distance (hormones)

15. 3 Stages of Cell Signaling: • Reception: Detection of a signal molecule (ligand) coming from outside the cell • Transduction: Convert signal to a form that can bring about a cellular response • Response: Cellular response to the signal molecule

16. Reception

17. Transduction

18. Response

19. Animation: Overview of Cell Signaling

20. Cell Signaling Video

21. 1. Reception • Binding between signal molecule (ligand) + receptor is highly specific. • Types of Receptors: • Plasma membrane receptor • water-soluble ligands • Intracellular receptors(cytoplasm, nucleus) • hydrophobic or small ligands • Eg. testosterone or nitric oxide (NO) • Ligand binds to receptor protein  protein changes SHAPE  initiates transduction signal

22. Plasma Membrane Receptors

23. G-Protein-Coupled Receptor

24. G-Protein-Coupled Receptor

25. Plasma Membrane Receptors

26. Receptor Tyrosine Kinase

27. Plasma Membrane Receptors

28. Ligand-Gated Ion Channel

29. Plasma Membrane Receptors

30. 2. Transduction • Cascades of molecular interactions relay signals from receptors  target molecules • Protein kinase: enzyme that phosphorylates and activates proteins at next level • Phosphorylation cascade: enhance and amplify signal

32. Second Messengers • small, nonprotein molecules/ions that can relay signal inside cell • Eg. cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3)

33. cAMP • cAMP = cyclic adenosine monophosphate • GPCR  adenylyl cyclase (convert ATP  cAMP)  activate protein kinase A

34. 3. Response • Regulate protein synthesis by turning on/off genes in nucleus (gene expression) • Regulate activity of proteins in cytoplasm

35. An Example of Cell Communication https://learn.genetics.utah.edu/content/cells/cellcom/

36. Signal Transduction Pathway Problems/Defects: Examples: • Diabetes • Cholera • Autoimmune disease • Cancer • Neurotoxins, poisons, pesticides • Drugs (anesthetics, antihistamines, blood pressure meds)

37. Cholera • Disease acquired by drinking contaminated water (w/human feces) • Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin • Toxin modifies G-protein involved in regulating salt & water secretion • G protein stuck in active form  intestinal cells secrete salts, water • Infected person develops profuse diarrhea and could die from loss of water and salts

38. Viagra • Used as treatment for erectile dysfunction • Inhibits hydrolysis of cGMP  GMP • Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis

39. Viagra inhibits cGMP breakdown

40. Apoptosis = cell suicide • Cell is dismantled and digested • Triggered by signals that activate cascade of “suicide” proteins (caspase) • Why? • Protect neighboring cells from damage • Animal development & maintenance • May be involved in some diseases (Parkinson’s, Alzheimer’s)

41. Apoptosis of a human white blood cell Left: Normal WBC Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

42. Effect of apoptosis during paw development in the mouse