Cell Communication

1. Cell Communication Chapter 7

2. 7.1 Cell Communication: An Overview • Cells communicate with one another through • Direct channels of communication • Specific contact between cells • Intercellular chemical messengers

3. Apoptosis Fig. 7-1, p. 140

4. Intercellular Chemical Messengers • Controlling cell • Releases signal molecule that causes response of target cells • Target cell processes signal in 3 steps: • Reception, transduction, response • Signal transduction • Series of events from reception to response

5. Signal Transduction Fig. 7-2, p. 142

6. Reception

7. 7.2 Cell Communication Systems with Surface Receptors • Peptide hormones and neurotransmitters • Primary extracellular signal molecules recognized by surface receptors in animals • Surface receptors • Integral membrane glycoproteins • Signaling molecule • Bound by a surface receptor • Triggers response pathways within the cell

8. Surface Receptors • Cell communication systems based on surface receptors have 3 components: (1) Extracellular signal molecules (2) Surface receptors that receive signals (3) Internal response pathways triggered when receptors bind a signal

9. Peptide Hormones • Peptide hormones • Small proteins • Growth factors • Special class of peptide hormones • Affect cell growth, division, differentiation

10. Neurotransmitters • Neurotransmitters include • Small peptides • Individual amino acids or their derivatives • Chemical substances

11. Surface Receptors • Surface receptors • Integral membrane proteins • Extend entirely through the plasma membrane • Binding of a signal molecule • Induces molecular change in the receptor that activates its cytoplasmic end

12. Response of Surface Receptor

13. Cellular Response Pathways (1) • Cellular response pathways • Operate by activating protein kinases • Protein kinases add phosphate groups • Stimulate or inhibit activities of target proteins, producing cellular response

14. Cellular Response Pathways (2) • Protein phosphatases • Reverse response • Remove phosphate groups from target proteins • Receptors are removed by endocytosis • When signal transduction is finished

15. Phosphorylation

16. Amplification • Each step of a response pathway catalyzed by an enzyme is amplified • Each enzyme activates hundreds or thousands of proteins that enter next step in pathway • Amplification • Allows full cellular response when few signal molecules bind to receptors

17. Amplification

18. 7.3 Surface Receptors with Built-In Protein Kinase Activity • Receptor Tyrosine Kinases

19. Receptor Tyrosine Kinases • Receptor tyrosine kinases bind signal molecule • Protein kinase site becomes active • Adds phosphate groups to tyrosines in the receptor itself, and to target proteins • Phosphate groups added to cytoplasmic end of receptor are recognition sites for proteins activated by binding to the receptor

20. Protein Kinase Activity

21. 7.4 G-Protein–Coupled Receptors • G proteins: Key molecular switches in second-messenger pathways • Two major G-protein–coupled receptor response pathways involve different second messengers

22. G-Protein-Coupled Receptors • G-protein-coupled receptors activate pathways • Binding of the extracellular signal molecule (first messenger) activates a site on the cytoplasmic end of the receptor

23. G-Protein-Coupled Receptors Fig. 7-8, p. 147

24. G-Protein Activation • Activated receptor turns on a G protein, which acts as a molecular switch • G protein • Active when bound to GTP • Inactive when bound to GDP

25. Active G Protein • Active G protein • Switches on the effector of the pathway (enzyme that generates second messengers) • Second messengers • Small internal signal molecules • Activate the protein kinases of the pathway

26. Response Pathways

27. Second Messengers: cAMP • 1st of two major pathways triggered by G-protein-coupled receptors • Effector (adenylyl cyclase) generates cAMP as second messenger • cAMP activates specific protein kinases

28. cAMP Receptor-Response Pathways Fig. 7-10, p. 148

29. cAMP Fig. 7-11, p. 148

30. Second Messengers: IP3 and DAG (1) • 2nd major pathway triggered by G-protein–coupled receptors • Activated effector (phospholipase C), generates two second messengers, IP3and DAG

31. Second Messengers: IP3 and DAG (2) • IP3 activates transport proteins in the ER • Releasing stored Ca2+ into the cytoplasm • Released Ca2+ (alone or with DAG) activates specific protein kinases • Adds phosphate groups to target proteins

32. IP3/DAG Receptor-Response Pathways

33. Pathway Controls • cAMP and IP3/DAG pathways are balanced by reactions that eliminate second messengers • Stopped by protein phosphatases that continually remove phosphate groups from target proteins • Stopped by endocytosis of receptors and their bound extracellular signals

34. Mutations • Mutated systems can turn on the pathways permanently, contributing to progression of some forms of cancer

35. Gene Regulation: Ras • Some pathways in gene regulation link certain receptor tyrosine kinases to a specific G protein (Ras) • When the receptor binds a signal molecule, it phosphorylates itself • Adapter proteins then bind, bridging to and activating Ras

36. Activated Ras • Activated Ras turns on the MAP kinase cascade • Last MAP kinase in cascade phosphorylates target proteins in the nucleus • Activates them to turn on specific genes • Many of these genes control cell division

37. Gene Regulation

38. 7.5 Pathways Triggered by Internal Receptors: Steroid Hormone Receptors • Steroid hormones have widely different effects • Depend on relatively small chemical differences • Response of a cell to steroid hormones • Depends on internal receptors and the genes they activate

39. Steroid Hormone Receptors • Steroid hormones penetrate plasma membrane • Bind to receptors within the cell • Internal receptors • Regulatory proteins that turn on specific genes when activated by binding a signal molecule • Produce cellular response

40. Two Domains of Steroid Hormone Receptors • Steroid hormone receptors • One domain recognizes and binds a specific steroid hormone • One domain interacts with the controlling regions of target genes

41. Gene Activation: Steroid Hormone Receptors

42. Cell Response • Cell response to a steroid hormone • Depends on whether it has an internal receptor for the hormone • Type of response within the cell • Depends on the genes that are recognized and turned on by an activated receptor

43. 7.6 Integration of Cell Communication Pathways • Cross talk

44. Cross-Talk • Cell signaling pathways communicate with one another to integrate responses to cellular signals • May result in a complex network of interactions between cell communication pathways

45. Cross-Talk

46. Modification of Cell Response • Cross-talk often results in • Modifications of cellular responses controlled by the pathways • Fine-tuning effects of combinations of signal molecules binding to receptors of a cell

47. Cell Communication PathwaysIn Animals • Inputs from other cellular response systems also can become involved in the cross-talk network • Cell adhesion molecules • Molecules arriving through gap junctions