1. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings PowerPoint ® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Chapter 11 Cell Communication

2. Overview: The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation The combined effects of multiple signals determine cell response For example, the dilation of blood vessels is controlled by multiple molecules Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Fig. 11-1

4. Concept 11.1: External signals are converted to responses within the cell Microbes let us look at the role of cell signaling in evolution Signal transduction pathway- series of steps that convert signals on the cell surface into a specific cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

5. Fig. 11-2 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

6. Similar pathways suggest ancestral signaling molecules evolved in prokaryotes and were modified in eukaryotes Ex. concentration of signaling molecules allows bacteria to detect population density Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

7. Fig. 11-3 Individual rod- shaped cells Spore-forming structure (fruiting body) Aggregation in process Fruiting bodies 0.5 mm 1 3 2

8. Local and Long-Distance Signaling Cells in multicellular organisms communicate by chemical messengers Animal and plant cells use cell junctions to directly connect cytoplasm of adjacent cells – In local signaling, animal cells may communicate by direct contact, or cell-cell recognition – OR animal cells communicate using local regulators- messenger molecules traveling short distances Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

9. Fig. 11-4 Plasma membranes Gap junctions between animal cells (a) Cell junctions Plasmodesmata between plant cells (b) Cell-cell recognition

10. 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 In long-distance signaling, plants and animals use chemicals called hormones

11. 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

12. Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell (c) Hormonal signaling

13. The Three Stages of Cell Signaling: A Preview Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes: – Reception – Transduction – Response Animation: Overview of Cell Signaling Animation: Overview of Cell Signaling Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

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

16. 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

17. Concept 11.2: Reception: A signal molecule binds to a receptor protein, causing it to change shape Binding between ligand (signal molecule) and receptor is highly specific – Shape change in receptor may be initial transduction of signal – Most signal receptors are plasma membrane proteins Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

18. Receptors in the Plasma Membrane Water-soluble signal molecules bind to specific sites on receptor proteins in plasma membrane Three main types of membrane receptors: – G protein-coupled receptors – Receptor tyrosine kinases – Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19. G protein-coupled receptor- plasma membrane receptor that works with the help of a G protein G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

20. Fig. 11-7a Signaling-molecule binding site Segment that interacts with G proteins G protein-coupled receptor

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. Receptor tyrosine kinases are membrane receptors attaching phosphates to tyrosines A receptor tyrosine kinase can trigger multiple signal transduction pathways at once Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

23. 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

24. Ligand-gated ion channel receptor acts as gate when receptor changes shape – Signal molecule binds as a ligand to the receptor, forming gate – gate allows specific ions, such as Na + or Ca 2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

25. Fig. 11-7d Signaling molecule (ligand) Gate closed Ions Ligand-gated ion channel receptor Plasma membrane Gate open Cellular response Gate closed 3 2 1

26. Intracellular Receptors Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

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

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

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

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

32. Concept 11.3: Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Signal transduction usually involves multiple steps Multistep pathways can amplify a signal: A few molecules can produce a large cellular response Multistep pathways provide more opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

33. Signal Transduction Pathways Relay molecules are mostly proteins Each 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 shape change in a protein Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

34. Protein Phosphorylation and Dephosphorylation In many pathways, signal is transmitted by a cascade of protein phosphorylations Protein kinases transfer phosphates from ATP to protein, a process called phosphorylation Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

35. Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation Phosphorylation & dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

36. 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

37. Small Molecules and Ions as Second Messengers Ligand or signal molecule binding to the receptor is the “first messenger” Second messengers- small, nonprotein, water-soluble molecules or ions that spread through a cell by diffusion 2 nd messengers act in paths. started by G protein-linked receptors and tyrosine kinase receptors – Cyclic AMP and calcium ions are common second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

38. Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal cAMP triggers a variety of responses Many signal molecules trigger formation of cAMP Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

39. Adenylyl cyclase Fig. 11-10 Pyrophosphate P P i ATP cAMP Phosphodiesterase AMP

40. Other components of cAMP pathways – G proteins, – G protein-coupled receptors, – protein kinases cAMP usually activates protein kinase A, which phosphorylates various other proteins Regulation: G-protein systems can also inhibit adenylyl cyclase Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

41. First messenger Fig. 11-11 G protein Adenylyl cyclase GTP ATP cAMP Second messenger Protein kinase A G protein-coupled receptor Cellular responses

42. Calcium Ions and Inositol Triphosphate (IP 3 ) Calcium ions (Ca 2+ ) act as 2 nd messengers – Calcium is important second messenger because cells can regulate its concentration A signal from a pathway may trigger increased calcium in the cytosol Pathways causing calcium release involve inositol triphosphate (IP 3 ) and diacylglycerol (DAG) as additional second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

43. EXTRACELLULAR FLUID Fig. 11-12 ATP Nucleus Mitochondrion Ca 2+ pump Plasma membrane CYTOSOL Ca 2+ pump Endoplasmic reticulum (ER) Ca 2+ pump ATP Key High [Ca 2+ ] Low [Ca 2+ ]

44. Fig. 11-13-1 EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein GTP G protein-coupled receptor Phospholipase C PIP 2 IP 3 DAG (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL

45. Fig. 11-13-2 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Ca 2+ (second messenger ) GTP

46. Fig. 11-13-3 G protein EXTRA- CELLULAR FLUID Signaling molecule (first messenger) G protein-coupled receptor Phospholipase C PIP 2 DAG IP 3 (second messenger) IP 3 -gated calcium channel Endoplasmic reticulum (ER) Ca 2+ CYTOSOL Various proteins activated Cellular responses Ca 2+ (second messenger ) GTP

47. Concept 11.4: Response: Cell signaling leads to regulation of transcription or cytoplasmic activities The cell’s response to an extracellular signal is the “output response” It may be nuclear or cytoplasmic Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

48. Nuclear and Cytoplasmic Responses Ultimately pathways lead to regulation of cellular activities response may be in cytoplasm or nucleus Many pathways regulate synthesis of enzymes or other proteins – These turn genes on or off in the nucleus – The final activated molecule may function as a transcription factor Other pathways regulate activity of enzymes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

49. Fig. 11-14 Growth factor Receptor Phosphorylatio n cascade Reception Transduction Active transcription factor Response P Inactive transcription factor CYTOPLASM DNA NUCLEUS mRNA Gene

50. Fig. 11-15 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)

51. Signaling pathways can also affect the physical characteristics of a cell like cell shape Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52. Fig. 11-16 RESULTS CONCLUSION Wild-type (shmoos)∆Fus3∆formin Shmoo projection forming Formin P Actin subunit P P Formin Fus3 Phosphory- lation cascade GTP G protein-coupled receptor Mating factor GDP Fus3 P Microfilament 1 2 3 4 5

53. Fine-Tuning of the Response Multistep pathways have two important benefits: – Amplifying the signal (and thus the response) – Contributing to the specificity of the response Amplification- At each step of an Enzyme cascade, the number of activated products is much more than the preceding step Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

54. The Specificity of Cell Signaling and Coordination of the Response Different cells have different kinds of proteins The different proteins let cells detect and respond to different signals Thus 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

55. 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.

56. Fig. 11-17a Signaling molecule Receptor Relay molecules Response 1 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses. Response 2 Response 3

57. Fig. 11-17b Response 4Response 5 Activation or inhibition Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

58. Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins- large relay proteins with other relay proteins attached – increase signal transduction efficiency by grouping different proteins involved in same pathway Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

59. Fig. 11-18 Signaling molecule Receptor Scaffolding protein Plasma membrane Three different protein kinases

60. Termination of the Signal Inactivation mechanisms are essential When signal molecules leave the receptor, it reverts to inactive state Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

61. Concept 11.5: Apoptosis (programmed cell death) integrates multiple cell-signaling pathways Apoptosis is programmed or controlled cell suicide A cell is chopped and packaged into vesicles that are digested by scavenger cells Apoptosis prevents enzymes from leaking out of a dying cell and damaging neighboring cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

62. Fig. 11-19 2 µm

63. Apoptosis in the Soil Worm Caenorhabditis elegans Apoptosis is important in shaping an organism during embryonic development Apoptosis in embryonic development was first studied in Caenorhabditis elegans In C. elegans, apoptosis results when specific proteins that accelerate apoptosis override those that stop apoptosis Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

64. Fig. 11-20 Ced-9 protein (active) inhibits Ced-4 activity Mitochondrion Receptor for death- Signaling molecule Ced-4 Ced-3 Inactive proteins (a) No death signal Ced-9 (inactive) Cell forms blebs Death- signaling molecule Other proteases Active Ced-4 Active Ced-3 Nucleases Activation cascade (b) Death signal

65. Apoptotic Pathways & Signals That Trigger Them Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by: – An extracellular death-signaling ligand – DNA damage in the nucleus – Protein misfolding in the endoplasmic reticulum Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

66. Apoptosis evolved early in animal evolution and is essential for the development and maintenance of all animals Apoptosis may be involved in some diseases – Parkinson’s – Alzheimer’s – interference with apoptosis may contribute to some cancers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

67. Fig. 11-21 Interdigital tissue 1 mm

68. Fig. 11-UN1 Reception Transduction Response Receptor Relay molecules Signaling molecule Activation of cellular response 1 2 3

69. Fig. 11-UN2

70. You should now be able to: 1.Describe the nature of a ligand-receptor interaction and state how such interactions initiate a signal-transduction system 2.Compare and contrast G protein-coupled receptors, tyrosine kinase receptors, and ligand- gated ion channels 3.List two advantages of a multistep pathway in the transduction stage of cell signaling 4.Explain how an original signal molecule can produce a cellular response when it may not even enter the target cell Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

71. 5.Define the term second messenger; briefly describe the role of these molecules in signaling pathways 6.Explain why different types of cells may respond differently to the same signal molecule 7.Describe the role of apoptosis in normal development and degenerative disease in vertebrates Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings