1. CHAPTER 11 CELL COMMUNICATION Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section A: An Overview of Cell Signaling 1.Cell signaling evolved early in the history of life 2. Communicating cells may be close together or far apart 3. The three stages of cell signaling are reception, transduction, and response

2. Communication is important for many unicellular organisms. Cell-to-cell communication is used multicellular organisms: for coordination. Biologists have discovered some universal mechanisms of cellular regulation. Cells may receive a variety of signals, chemical signals, electromagnetic signals, and mechanical signals. Introduction Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

3. The process of surface signaling leading to a specific cellular response is called a signal- transduction pathway. They convert signals on a cell ’ s surface into cellular responses through a series of steps Signaling molecules evolved first in ancient prokaryotes were then adopted for new uses by single-celled eukaryotes and multicellular descendents. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

4. Receptor  factor a factor a   a Exchange of mating factors Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell a/  1 2 3

5. Signaling molecules can target other cells. 1.Some cells release local regulators that influence cells close by. Paracrine signaling occurs when numerous cells can receive and respond to growth factors produced by a cell nearby. This is a generalized release. 2. Communicating cells may be close together or far apart Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.3a1

6. In synaptic signaling, a nerve cell produces a neurotransmitter that diffuses to a single cell that is almost touching the sender. This is a specific release. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.3a2 2. Plants and animals use hormones to signal at greater distances. In animals, hormones effect target cells specifically. In plants, hormones usually travel from cell to cell or by diffusion in air.

7. Fig. 11-5 Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid (a) Paracrine signaling(b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

8. Fig. 11-5ab Local signaling Target cell Secretory vesicle Secreting cell Local regulator diffuses through extracellular fluid (a) Paracrine signaling (b) Synaptic signaling Target cell is stimulated Neurotransmitter diffuses across synapse Electrical signal along nerve cell triggers release of neurotransmitter

9. 3. Cells may communicate by direct contact. Signaling substances dissolved in the cytosol pass freely between adjacent cells. Cells may also communicate via direct contact between substances on their surfaces. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.4

10. Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

11. The process involves three stages.The process involves three stages 1.In reception, a chemical signal binds to a cellular protein, typically at the cell’s surface. 2.In transduction, binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway. 3.In response, the transduced signal triggers a specific cellular activity. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.5 3. The three stages of cell signaling are reception, transduction, and response

12. Fig. 11-6-1 Reception 1 EXTRACELLULAR FLUID Signaling molecule Plasma membrane CYTOPLASM 1 Receptor

13. Fig. 11-6-2 1 EXTRACELLULAR FLUID Signaling molecule Plasma membrane CYTOPLASM Transduction 2 Relay molecules in a signal transduction pathway Reception 1 Receptor

14. Fig. 11-6-3 EXTRACELLULAR FLUID Plasma membrane CYTOPLASM Receptor Signaling molecule Relay molecules in a signal transduction pathway Activation of cellular response TransductionResponse 2 3 Reception 1

15. CHAPTER 11 CELL COMMUNICATION Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section B: Signal Reception and the Initiation of Transduction 1.A signal molecule binds to a receptor protein, causing the protein to change shape 2. Most signal receptors are plasma membrane proteins

16. A cell targeted by a chemical signal has a receptor protein that recognizes the signal molecule (ligand). There are three main types of membrane receptors: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors 1. A signal molecule binds to a receptor protein Section B: Signal Reception and the Initiation of Transduction

17. G-protein receptors: Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings A G-protein-linked receptor is a receptor protein with a G-protein on the cytoplasmic side. It has seven alpha helices in the membrane. Examples of signal molecules include hormones, and neurotransmitters.

18. Signaling-molecule binding site Segment that interacts with G proteins G protein-coupled receptor

19. The G protein acts as an on-off switch. The G-protein system cycles between on and off. When activated with signal molecule, the receptor binds to an inactive G protein in membrane. The G protein then binds with another membrane protein, often an enzyme, and lead to a cellular response. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.7a

20. The whole system can be shut down quickly when the extracellular signal molecule is no longer present. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings G-protein systems are extremely widespread and diverse. They can play an important role during embryonic development and sensory systems. Similarities among G-protein-linked receptors suggest that this signaling system evolved very early.

21. Fig. 11-7b G protein-coupled receptor Plasma membrane Enzyme G protein (inactive) GDP CYTOPLASM Activated enzyme GTP Cellular response GDP P i Activated receptor GDP GTP Signaling molecule Inactive enzyme 1 2 3 4

22. The tyrosine-kinase receptor system is especially effective when the cell needs to coordinate a many activities at once. Extracellular growth factors often bind to tyrosine- kinase receptors. The cytoplasmic side is a tyrosine kinase, (this means it transfers a phosphate group from ATP to tyrosine on a substrate protein.) Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Tyrosine-kinase receptors:

23. An individual tyrosine-kinase receptor consists of several parts: an outside signal-binding sites, a single alpha helix spanning the membrane, and an intracellular tail with several tyrosines. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.8a

24. Fig. 11-7c Signaling molecule (ligand) Ligand-binding site  Helix Tyrosines Tyr Receptor tyrosine kinase proteins CYTOPLASM Signaling molecule Tyr Dimer Activated relay proteins Tyr P P P P P P Cellular response 1 Cellular response 2 Inactive relay proteins Activated tyrosine kinase regions Fully activated receptor tyrosine kinase 6 6 ADP ATP Tyr P P P P P P 1 2 3 4

25. When 2 ligands bind to 2 receptors, they get together forming a dimer. This activates the tyrosine-kinase of both. These add phosphates to the tyrosines Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.8b The fully-activated receptor proteins activate a variety of specific relay proteins that bind to specific phosphorylated tyrosine molecules. One tyrosine-kinase receptor dimer may activate ten or more different intracellular proteins simultaneously.

26. Acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor Ligand-gated ion channels:

27. Other signal receptors are dissolved in the cytosol or nucleus of target cells. The signals pass through the plasma membrane. These chemical messengers include the hydrophobic steroid and thyroid hormones of animals. Also in this group is nitric oxide (NO), a gas whose small size allows it to slide between membrane phospholipids. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Intracellular Receptors:

28. Testosterone, like other hormones, travels through the blood throughout the body. In the cytosol, they bind and activate receptor proteins. These activated proteins enter the nucleus and turn on genes that control male sex characteristics. Notice these travel inside the cell. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.10

29. Fig. 11-8-1 Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID DNA NUCLEUS CYTOPLASM

30. Fig. 11-8-2 Receptor protein Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

31. Fig. 11-8-3 Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM

32. Fig. 11-8-4 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM

33. Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS New protein CYTOPLASM

34. These activated proteins act as transcription factors. These control which genes are turned on /transcribed Some intracellular receptors are already in the nucleus and bind to the signal molecules there (e.g., estrogen receptors). Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

35. CHAPTER 11 CELL COMMUNICATION Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section C: Signal-Transduction Pathways 1.Pathways relay signals from receptors to cellular responses 2. Protein phosphorylation, a common mode of regulation in cells, is a major mechanism of signal transduction 3. Certain small molecules and ions are key components of signaling pathways (second messengers)

36. The transduction stage of signaling is usually a multistep pathway. These pathways often greatly amplify the signal. A small number of signal molecules can produce a large cellular response. Also, multistep pathways provide more opportunities for coordination and regulation than do simpler systems. Introduction Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section C: Signal-Transduction Pathways

37. Signal-transduction pathways act like falling dominoes. The original signal molecule is not passed along the pathway and may not even enter the cell. Its information is passed on. At each step the signal is transduced into a different form, often by a conformational change in a protein. 1. Pathways relay signals from receptors to cellular responses Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

38. In many pathways, the signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Many of the relay molecules in a signal-transduction pathway are protein kinases that lead to a “phosphorylation cascade”. Each protein phosphorylation leads to a shape change. 2. Protein phosphorylation: Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

39. Fig. 11.11

40. Phosphorylation of a protein typically converts it from an inactive form to an active form. A single cell may have hundreds of different protein kinases, each specific for a different substrate protein. Abnormal activity of protein kinases can cause abnormal cell growth and contribute to the development of cancer. Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

41. Protein phosphatases: These enzymes rapidly remove phosphate groups from proteins. The activity of a protein regulated by phosphorylation depends on the balance of active kinase molecules (ON) and active phosphatase molecules (OFF). Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

42. Fig. 11-9 Signaling molecule Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP ADP Active protein kinase 2 P P PP Inactive protein kinase 3 ATP ADP Active protein kinase 3 P P PP i ATP ADP P Active protein PP P i Inactive protein Cellular response Phosphorylation cascade i

43. Many signaling pathways involve small, nonprotein, water-soluble molecules or ions, called second messengers. These molecules rapidly diffuse throughout the cell. Second messengers participate in pathways initiated by both G-protein-linked receptors and tyrosine- kinase receptors. 2 of the most important are cyclic AMP (cAMP) & Ca 2+. 3. Small signal molecules and ions are secondary messengers of signaling pathways. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

44. Many hormones and other signals trigger the formation of cAMP. Binding by the signal to a receptor activates a G protein activates an enzyme on the plasma membrane. The cAMP from the this enzyme diffuses through the cell and activates a protein kinase A which phosphorylates other proteins. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.13

45. Many signal molecules in animals induce responses in their target cells via signal- transduction pathways that increase the cytoplasmic concentration of Ca 2+. In animal cells, increases in Ca 2+ may cause contraction of muscle cells for example. In plant cells, increases in Ca 2+ trigger responses for coping with environmental stress, like drought. Cells use Ca 2+ as a second messenger in both G- protein pathways and tyrosine-kinase pathways.

46. Many signal molecules in animals induce responses in their target cells via signal- transduction pathways that increase the cytoplasmic concentration of Ca 2+. In animal cells, increases in Ca 2+ may cause contraction of muscle cells for example. In plant cells, increases in Ca 2+ trigger responses for coping with environmental stress, like drought. Cells use Ca 2+ as a second messenger in both G- protein pathways and tyrosine-kinase pathways. Video Wrap-up! Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

47. CHAPTER 11 CELL COMMUNICATION Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Section D: Cellular Responses to Signals 1.In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus 2. Elaborate pathways amplify and specify the cell’s response to signals

48. Ultimately, a signal-transduction pathway leads to the regulation of one or more cellular activities. This may be a change in an ion channel or a change in cell metabolism. For example, epinephrine helps regulate cellular energy metabolism by activating enzymes that catalyze the breakdown of glycogen. 1. In response to a signal, a cell may regulate activities in the cytoplasm or transcription in the nucleus Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

49. The stimulation of glycogen breakdown by epinephrine involves a G-protein-linked receptor, a G Protein adenylyl cyclase and cAMP, and several protein kinases before glycogen phosphorylase is activated. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.16

50. Other signaling pathways do not regulate the activity of enzymes but the synthesis of enzymes or other proteins. Activated receptors may act as transcription factors that turn specific genes on or off in the nucleus. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 11.17

51. As important as activating mechanisms are inactivating mechanisms. For a cell to remain alert and capable of responding to incoming signals, each molecular change in its signaling pathways must last only a short time. Binding of signal molecules to receptors must be reversible, allowing the receptors to return to their inactive state when the signal is released. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings

52. The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins These different proteins allow cells to detect and respond to different signals Even the same signal can have different effects in cells with different proteins and pathways Pathway branching and “cross-talk” further help the cell coordinate incoming signals Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

53. Fig. 11-17 Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2 Response 3 Cell B. Pathway branches, leading to two responses. Response 4 Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.