1. LECTURE PRESENTATIONS For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson © 2011 Pearson Education, Inc. Lectures by Erin Barley Kathleen Fitzpatrick Cell Communication Chapter 11

2. Overview: Cellular Messaging _______________________ is essential for both multicellular and unicellular organisms Biologists have discovered some universal mechanisms of cellular regulation Cells most often communicate with each other via _______________ __________________ For example, the fight-or-flight response is triggered by a signaling molecule called ___________________________ © 2011 Pearson Education, Inc.

3. Figure 11.1

4. Concept 11.1: External signals are converted to responses within the cell ______________ provide a glimpse of the role of cell signaling in the evolution of life © 2011 Pearson Education, Inc.

5. Evolution of Cell Signaling The yeast, Saccharomyces cerevisiae, has two mating types, ___________________ Cells of different mating types locate each other via __________ ________ specific to each type A __________ _______ _______________ is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response Signal transduction pathways convert signals on a _________ _____________ into cellular responses © 2011 Pearson Education, Inc.

6. Figure 11.2 Exchange of mating factors Receptor  factor a factor Yeast cell, mating type a Yeast cell, mating type  Mating New a/  cell 1 2 3 a a a/   

7. Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The __________________ of signaling molecules allows bacteria to sense local population density © 2011 Pearson Education, Inc.

8. Individual rod-shaped cells Spore-forming structure (fruiting body) Aggregation in progress Fruiting bodies 1 2 3 0.5 mm 2.5 mm Figure 11.3

9. Local and Long-Distance Signaling Cells in a multicellular organism communicate by ______________ messengers Animal and plant cells have _____ ____________ that directly connect the cytoplasm of adjacent cells In __________ signaling, animal cells may communicate by ___________ ___________, or ________________ _______________________ © 2011 Pearson Education, Inc.

10. Figure 11.4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions (b) Cell-cell recognition

11. In many other cases, animal cells communicate using _________ ____________, messenger molecules that travel only _________ distances In long-distance signaling, plants and animals use chemicals called ______________ The ability of a cell to respond to a signal depends on whether or not it has a ____________ specific to that signal © 2011 Pearson Education, Inc.

12. Figure 11.5a Local signaling Target cell Secreting cell Secretory vesicle Local regulator diffuses through extracellular fluid. (a) Paracrine signaling (b) Synaptic signaling Electrical signal along nerve cell triggers release of neurotransmitter. Neurotransmitter diffuses across synapse. Target cell is stimulated.

13. Figure 11.5b Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream. Target cell specifically binds hormone. (c) Endocrine (hormonal) signaling

14. The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone ______________ acts on cells Sutherland suggested that cells receiving signals went through three processes –_____________ © 2011 Pearson Education, Inc.

15. Animation: Overview of Cell Signaling Right-click slide / select “Play”

16. Figure 11.6-1 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM Reception Receptor Signaling molecule 1

17. Figure 11.6-2 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM ReceptionTransduction Receptor Signaling molecule Relay molecules in a signal transduction pathway 2 1

18. Figure 11.6-3 Plasma membrane EXTRACELLULAR FLUID CYTOPLASM ReceptionTransduction Response Receptor Signaling molecule Activation of cellular response Relay molecules in a signal transduction pathway 3 2 1

19. Concept 11.2: Reception: A signaling molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (_______) and receptor is highly ________________ A _________ ______________ in a receptor is often the initial transduction of the signal Most signal receptors are ______________ ______________ ____________________ © 2011 Pearson Education, Inc.

20. Receptors in the Plasma Membrane Most ___________ ___________ ____________ bind to specific sites on receptor proteins that span the plasma membrane There are three main types of membrane receptors –_______________________ © 2011 Pearson Education, Inc.

21. _________________________________ are the largest family of cell-surface receptors A GPCR is a plasma membrane receptor that works with the help of a ____ ______________ The G protein acts as an ______________: If _____________ is bound to the G protein, the G protein is __________________ © 2011 Pearson Education, Inc.

22. Figure 11.7a G protein-coupled receptor Signaling molecule binding site Segment that interacts with G proteins

23. Figure 11.7b G protein-coupled receptor 21 3 4 Plasma membrane G protein (inactive) CYTOPLASM Enzyme Activated receptor Signaling molecule Inactive enzyme Activated enzyme Cellular response GDP GTP GDP GTP P i GDP

24. Figure 11.8 Plasma membrane Cholesterol  2 -adrenergic receptors Molecule resembling ligand

25. __________ ____________ _______________ are membrane receptors that attach phosphates to tyrosines A receptor tyrosine kinase can trigger _________ ____________ ________________ __________ at once Abnormal functioning of RTKs is associated with many types of ________________ © 2011 Pearson Education, Inc.

26. Figure 11.7c Signaling molecule (ligand) 2 1 34 Ligand-binding site  helix in the membrane Tyrosines CYTOPLASM Receptor tyrosine kinase proteins (inactive monomers) Signaling molecule Dimer Tyr P P P P P P P P P P P P Activated tyrosine kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine kinase (phosphorylated dimer) Activated relay proteins Cellular response 1 Cellular response 2 Inactive relay proteins 6 ATP 6 ADP

27. A ____________________________ receptor 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 _________________, through a channel in the receptor © 2011 Pearson Education, Inc.

28. Figure 11.7d Signaling molecule (ligand) 2 1 3 Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed

29. Intracellular Receptors ______________ ___________ __________ are found in the cytosol or nucleus of target cells _________ __________ _______________ can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the ______________________________ of animals An activated hormone-receptor complex can act as a _____________ _____________, turning on specific genes © 2011 Pearson Education, Inc.

30. Figure 11.9-1 Hormone (testosterone) Receptor protein Plasma membrane DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID

31. Figure 11.9-2 Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID

32. Figure 11.9-3 Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID

33. Figure 11.9-4 Hormone (testosterone) Receptor protein Plasma membrane Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM EXTRACELLULAR FLUID

34. Figure 11.9-5 Hormone (testosterone) Receptor protein Plasma membrane EXTRACELLULAR FLUID Hormone- receptor complex DNA mRNA NUCLEUS CYTOPLASM New protein

35. Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves _____________ __________ Multistep pathways can ___________ _ _______: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response © 2011 Pearson Education, Inc.

36. Signal Transduction Pathways The molecules that relay a signal from receptor to response are mostly ___________ Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated At each step, the signal is transduced into a different form, usually a __________ __________ in a protein © 2011 Pearson Education, Inc.

37. Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of ____________ _______________ ____________________ transfer phosphates from ATP to protein, a process called __________________ © 2011 Pearson Education, Inc.

38. ____________ _____________ remove the phosphates from proteins, a process called ________________________ This phosphorylation and dephosphorylation system acts as a _____________ __________, turning activities on and off or up or down, as required © 2011 Pearson Education, Inc.

39. Receptor Signaling molecule Activated relay molecule Phosphorylation cascade Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein Cellular response ATP ADP ATP ADP ATP ADP PP P P P P i Figure 11.10

40. Activated relay molecule Phosphorylation cascade Inactive protein kinase 1 Active protein kinase 1 Active protein kinase 2 Active protein kinase 3 Inactive protein kinase 2 Inactive protein kinase 3 Inactive protein Active protein ATP ADP ATP ADP ATP ADP PP P P P i P Figure 11.10a

41. Small Molecules and Ions as Second Messengers The extracellular signal molecule (ligand) that binds to the receptor is a pathway’s “__________ ______________” __________ _____________ are small, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by _________________________ ________________________________ are common second messengers © 2011 Pearson Education, Inc.

42. Cyclic AMP ___________________ is one of the most widely used second messengers _____________ ____________, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal © 2011 Pearson Education, Inc.

43. Figure 11.11 Adenylyl cyclase Phosphodiesterase Pyrophosphate AMP H2OH2O ATP P i P cAMP

44. Many signal molecules trigger formation of _____ Other components of cAMP pathways are _____ ________________________________________ cAMP usually activates ___________ _____________, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that ____________ ________________________________________ © 2011 Pearson Education, Inc.

45. Figure 11.12 G protein First messenger (signaling molecule such as epinephrine) G protein-coupled receptor Adenylyl cyclase Second messenger Cellular responses Protein kinase A GTP ATP cAMP

46. Calcium Ions and Inositol Triphosphate (IP 3 ) ___________ _______________ act as a second messenger in many pathways Calcium is an important second messenger because cells can ________________ ___ ________________ © 2011 Pearson Education, Inc.

47. Figure 11.13 Mitochondrion EXTRACELLULAR FLUID Plasma membrane Ca 2  pump Nucleus CYTOSOL Ca 2  pump Endoplasmic reticulum (ER) ATP Low [Ca 2  ] High [Ca 2  ] Key

48. A signal relayed by a signal transduction pathway may trigger an increase in calcium in the cytosol Pathways leading to the release of calcium involve _____________________________ and _____________________________ as additional second messengers © 2011 Pearson Education, Inc.

49. Animation: Signal Transduction Pathways Right-click slide / select “Play”

50. G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca 2  GTP Figure 11.14-1

51. Figure 11.14-2 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Ca 2  (second messenger) Ca 2  GTP

52. Figure 11.14-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C DAG PIP 2 IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) CYTOSOL Various proteins activated Cellular responses Ca 2  (second messenger) Ca 2  GTP

53. Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities The cell’s response to an extracellular signal is sometimes called the “___________ __________” © 2011 Pearson Education, Inc.

54. Nuclear and Cytoplasmic Responses Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the ____________ or in the ______________ Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning ________________________ in the nucleus The final activated molecule in the signaling pathway may function as a ______________ __________________ © 2011 Pearson Education, Inc.

55. Figure 11.15 Growth factor Receptor Reception Transduction CYTOPLASM Response Inactive transcription factor Active transcription factor DNA NUCLEUS mRNA Gene Phosphorylation cascade P

56. Other pathways regulate the activity of _________________ rather than their synthesis © 2011 Pearson Education, Inc.

57. Figure 11.16 Reception Transduction Response Binding of epinephrine to G protein-coupled receptor (1 molecule) Inactive G protein Active G protein (10 2 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (10 2 ) ATP Cyclic AMP (10 4 ) Inactive protein kinase A Active protein kinase A (10 4 ) Inactive phosphorylase kinase Active phosphorylase kinase (10 5 ) Inactive glycogen phosphorylase Active glycogen phosphorylase (10 6 ) Glycogen Glucose 1-phosphate (10 8 molecules)

58. Signaling pathways can also affect the overall _____________ __ __ _________, for example, changes in cell ____________ © 2011 Pearson Education, Inc.

59. Wild type (with shmoos)  Fus3  formin Mating factor activates receptor. Mating factor G protein-coupled receptor Shmoo projection forming Formin G protein binds GTP and becomes activated. 2 1 3 4 5 P P P P Formin Fus3 GDP GTP Phosphory- lation cascade Microfilament Actin subunit Phosphorylation cascade activates Fus3, which moves to plasma membrane. Fus3 phos- phorylates formin, activating it. Formin initiates growth of microfilaments that form the shmoo projections. RESULTS CONCLUSION Figure 11.17

60. Fine-Tuning of the Response There are four aspects of fine-tuning to consider –______________ ___ __ ____________ (and thus the response) –___________________ of the response –Overall ______________ __ ____________, enhanced by _______________ _____________ –___________________ of the signal © 2011 Pearson Education, Inc.

61. Signal Amplification _______________ __________ amplify the cell’s response At each step, the number of activated products is much _____________ than in the preceding step © 2011 Pearson Education, Inc.

62. The Specificity of Cell Signaling and Coordination of the Response Different kinds of cells have different collections of proteins These _____________ ____________ allow cells to detect and respond to different signals Even the same signal can have different effects in cells with different proteins and pathways _________________________________ further help the cell coordinate incoming signals © 2011 Pearson Education, Inc.

63. Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Response 2Response 3 Cell B. Pathway branches, leading to two responses. Figure 11.18a

64. Response 4 Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response. Figure 11.18b

65. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes _____________ ______________ are large relay proteins to which other relay proteins are attached Scaffolding proteins can increase the signal transduction ____________ by grouping together different proteins involved in the same pathway In some cases, scaffolding proteins may also help ________________ some of the relay proteins © 2011 Pearson Education, Inc.

66. Figure 11.19 Signaling molecule Receptor Plasma membrane Scaffolding protein Three different protein kinases

67. Termination of the Signal __________________ _____________ are an essential aspect of cell signaling If ___________ _____________ falls, fewer receptors will be bound Unbound receptors revert to an __________ ____ © 2011 Pearson Education, Inc.

68. Concept 11.5: Apoptosis integrates multiple cell-signaling pathways _________________ is programmed or controlled cell suicide Components of the cell are chopped up and packaged into vesicles that are digested by scavenger cells Apoptosis prevents ______________________ of a dying cell and damaging neighboring cells © 2011 Pearson Education, Inc.

69. Figure 11.20 2  m

70. Apoptosis in the Soil Worm Caenorhabditis elegans Apoptosis is important in shaping an organism during ______________ _________________ The role of apoptosis in embryonic development was studied in Caenorhabditis elegans In C. elegans, apoptosis results when proteins that “accelerate” apoptosis override those that “put the brakes” on apoptosis © 2011 Pearson Education, Inc.

71. Figure 11.21a Mitochondrion Ced-9 protein (active) inhibits Ced-4 activity Receptor for death- signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal

72. Death- signaling molecule Ced-9 (inactive) Cell forms blebs Active Ced-4 Active Ced-3 Other proteases Nucleases Activation cascade (b) Death signal Figure 11.21b

73. Apoptotic Pathways and the Signals That Trigger Them _____________ are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by –An ______________ ___________ ___________ –__________ ____________ in the nucleus –___________ ___________________ in the endoplasmic reticulum © 2011 Pearson Education, Inc.

74. Apoptosis evolved early in animal evolution and is essential for the __________________ ____ ________________ of all animals Apoptosis may be involved in some diseases (for example, ____________ ___ _____________); interference with apoptosis may contribute to some _______________ © 2011 Pearson Education, Inc.

75. Figure 11.22 Interdigital tissue Cells undergoing apoptosis Space between digits 1 mm