1. www.cengage.com/biology/solomon Albia Dugger Miami Dade College Eldra Solomon Linda Berg Diana W. Martin Chapter 6 Cell Communication

2. Cell-to-Cell Communication

3. Communication Between Cells To maintain homeostasis, cells of a multicellular organism must continuously communicate with one another Organisms of different species, and even different kingdoms and domains, communicate with one another by chemical signals

4. 6.1 CELL COMMUNICATION: AN OVERVIEW LEARNING OBJECTIVE: Describe the four main processes essential for cells to communicate

5. Cell Signaling cell signaling Mechanisms by which cells communicate with one another Four main processes: 1.A cell sends a signal 2.Signal reception 3.Signal transduction 4.Response

6. A Cell Sends a Signal In chemical signaling, a cell must synthesize and release signaling molecules If the cells that can respond to the signal (target cells) are not nearby, the signal must be transported to them (usually by a circulatory system)

7. Reception of the Signal Receptors are large proteins or glycoproteins that bind with specific signaling molecules Many types of signaling molecules bind to receptors on the surface of the target cell, and do not actually enter the cell

8. Signal Transduction Signal transduction is the process by which a cell converts an extracellular signal into an intracellular signal, and relays the signal, leading to a cellular response Typically involves a chain of molecules that relay information

9. Response to the Signal The final molecule in the signaling pathway converts the signal into a response that alters some cell process Many signaling molecules stimulate ion channels in the plasma membrane to open or close – others activate or inhibit specific genes in the nucleus After a signaling molecule has done its job, its action must be stopped – certain mechanisms operate to terminate the signal

10. Overview of Cell Signaling

11. Fig. 6-2, p. 136 Signaling molecules Receptor Signaling molecule A Signaling molecule B Target cell Signaling molecule C Protein that regulates a gene ProteinEnzyme Altered membrane permeability Change in some metabolic process Specific gene activated or repressed 1 2 3 4

12. ANIMATION: Signal transduction To play movie you must be in Slide Show Mode PC Users: Please wait for content to load, then click to play Mac Users: CLICK HERECLICK HERE

13. KEY CONCEPTS 6.1 Cells communicate by signaling one another, a complex process that involves production of signaling molecules, reception of the signal, signal transduction, and a response

14. 6.2 SENDING SIGNALS LEARNING OBJECTIVE: Compare three types of signaling molecules: neurotransmitters, hormones, and local regulators

15. Ways Cells Communicate Cells communicate in several ways: Directly through cell junctions Electrical signals Temporary cell-to-cell contact Chemical signals

16. Types of Chemical Signals Neurons release chemical compounds (neurotransmitters) that diffuse across gaps (synapses) between neurons Chemical compounds displayed on the surface of certain immune system cells allow cells to recognize and communicate with one another by making direct contact Endocrine glands secrete hormones that are transported by the blood to target cells

17. Types of Chemical Signals (cont.) Some cells produce local regulators that diffuse through the interstitial fluid surrounding the cells, and act on nearby cells (paracrine regulation) Local regulators include local chemical mediators: Growth factors stimulate cell division and development Histamine causes blood vessels to dilate Nitric oxide (NO) relaxes smooth muscle in blood vessel walls Prostaglandins help regulate metabolic activities

18. Types of Cell Signaling

19. Fig. 6-3a, p. 137 (a) Neurons transmit signals across synapses. Receptor Signaling molecules Target neuron Signaling neuron

20. Fig. 6-3b, p. 137 (b) Some cells signal one another by making direct contact. Receptor Nucleus Signaling cell Target cell

21. Fig. 6-3c, p. 137 Signaling molecules (hormone) Receptor (c) Many hormones are transported by the blood to target cells. Endocrine cell Hormone transported in blood Target cell

22. Fig. 6-3d, p. 137 (d) In paracrine regulation, a local regulator diffuses to target cells. Signaling molecules (local regulator) Receptor Signaling cell Target cell

23. KEY CONCEPTS 6.2 Cells signal one another using chemical compounds such as neurotransmitters, hormones, and other signaling molecules

24. 6.3 RECEPTION LEARNING OBJECTIVES: Identify mechanisms that make reception a highly specific process Briefly compare ion channel–linked receptors, G protein– linked receptors, enzyme-linked receptors, and intracellular receptors

25. Receptors Cells are exposed to hundreds of types of signaling molecules – the signals a cell responds to depends on its receptors A signaling molecule (ligand) binds to a specific receptor and triggers a biological response Hydrophilic molecules bind to protein receptors on the surface of target cells Hydrophobic molecules move through the plasma membrane and bind with intracellular receptors

26. Cell-Surface and Intracellular Receptors

27. Fig. 6-4a, p. 138 Receptor Signaling molecules Nucleus (a) Hydrophilic signaling molecules bind to receptors in the plasma membrane.

28. Fig. 6-4b, p. 138 Signaling molecules Receptor (b) Hydrophobic signaling molecules cross the plasma membrane and bind with receptors inside the cell.

29. Specialization Only the signaling molecule that fits the shape of a specific receptor can trigger a response in a cell Different cell types produce different receptors A cell may synthesize many different kinds of receptors, which may differ with conditions or stages in its life cycle The same signal can have different meanings for various target cells

30. Other Receptors Some receptors respond to non-chemical signals: Rhodopsin (in vertebrate eyes) is activated by light Phytochromes (in plants) are activated by red light

31. Cells Regulate Reception Cells regulate reception by increasing or decreasing the number of each type of receptor Receptor up-regulation increases the number of receptors synthesized, and amplifies the signaling molecule’s effect Receptor down-regulation often involves transporting receptors to lysosomes, where they are destroyed

32. Three Types of Surface Receptors (1) Ion channel-linked receptors (ligand-gated channels) Found in the plasma membrane Convert chemical signals into electrical signals Ion channel opens or closes in response to binding of the signaling molecule (ligand) Example: acetylcholine (a neurotransmitter) binds to and opens a ligand-gated sodium ion channel

33. Ion Channel–Linked Receptor

34. Fig. 6-5a, p. 140 Signaling molecule Extracellular fluid Na + Receptor Cytosol (a) Ion channel–linked receptor 12

35. Three Types of Surface Receptors (2) G protein-linked receptors (G protein-coupled receptors) Transmembrane proteins with a binding site for a signaling molecule on the outside, and a binding site for a specific G protein that extends into the cytosol Couple signaling molecules to signal transduction pathways inside the cell More than 400 G protein–linked receptors are potential targets for pharmaceutical interventions

36. G Protein–Linked Receptor

37. Fig. 6-5b, p. 140 Signaling molecule Receptor G proteinEnzyme Cytosol GDP GTP (b) G protein–linked receptor 12

38. Three Types of Surface Receptors (3) Enzyme-linked receptors Transmembrane proteins with a binding site for a signaling molecule outside the cell and an enzyme component inside the cell (Example: tyrosine kinases) Bind hormones such as insulin and growth factors Enzyme-Linked Receptors in Plants Ethylene Regulates seed germination and ripening of fruit

39. Enzyme-Linked Receptors

40. Receptors Inside the Cell Intracellular receptors are found in the cytosol or nucleus – most are transcription factors that regulate expression of specific genes Signaling molecules are small, hydrophobic molecules that diffuse across the membranes of target cells Some combine with receptors in the cytosol, then move into the nucleus (e.g. steroid hormones) Some bind to receptors already bound to DNA inside the nucleus (e.g. thyroid hormones)

41. KEY CONCEPTS 6.3 A signaling molecule binds to a receptor molecule on the cell surface or inside the target cell

42. 6.4 SIGNAL TRANSDUCTION LEARNING OBJECTIVES: Compare the actions of the main types of receptors in signal transduction Trace the sequence of events in signal transduction for each of the following second messengers: cyclic AMP, inositol trisphosphate, diacylglycerol, and calcium ions

43. A Signal Transduction Pathway Many regulatory molecules activate membrane proteins which then transduce the signal A signaling molecule binds with a cell-surface receptor and activates it by changing the shape of the receptor tail that extends into the cytoplasm The signal is relayed through a chain of intracellular signaling molecules (protein kinases) which make up a signaling pathway (signaling cascade) that amplifies the signal

44. Molecular Switches Each component in a signaling pathway acts as a molecular “switch” which can be active (“on”) or inactive (“off ”) Every activated molecule in a signaling pathway must be inactivated in order to transmit a new signal Molecular switches are typically regulated by the addition or removal of phosphate groups

45. Molecular Switches (cont.) protein kinase cascade Signaling pathway in which a series of protein kinase molecules are phosphorylated phosphatase Enzyme that catalyzes the removal of a phosphate group by hydrolysis (dephosphorylation) Protein phosphatases help regulate protein kinase cascades

46. A Phosphorylation Cascade

47. Fig. 6-6, p. 142 Signaling molecule Receptor Active protein kinase 1 Inactive protein kinase 1 Active protein kinase 2 Inactive protein kinase 2 Active protein kinase 3 Inactive protein kinase 3 Active protein Inactive protein Alters some cell process 1 2 3 4 5

48. Ion Channel-Linked Receptors Many ion channel gates remain closed until a ligand binds to the receptor Gamma-aminobutyric acid (GABA) receptors bind the neurotransmitter GABA Ligand-gated chloride ion channels GABA inhibits neural signaling when chloride ions leave the cell, which inhibits transmission of neural impulses

49. G Protein-Linked Receptors G protein-linked receptors activate G proteins that regulate many signal transduction pathways In its inactive state, the G protein has one subunit linked to guanosine diphosphate (GDP) When a signaling molecule binds to the receptor, GDP is replaced by guanosine triphosphate (GTP) GTP releases energy, and the G protein is deactivated The signaling molecule acts as the first messenger, and information is relayed by the G protein to a second messenger

50. Second Messengers second messengers Ions or small molecules that amplify signals inside the cell and relay them to other signaling or target proteins Produced in large quantities when receptors are activated The last molecule in the signaling chain activates the final response Example: cyclic AMP

51. Cyclic AMP Production When a stimulatory G protein undergoes a conformational change, it binds and activates adenylyl cyclase Activated adenylyl cyclase catalyzes the production of cyclic AMP (cAMP) from ATP The pathway is inactivated by phosphodiesterase, which converts cAMP to adenosine monophosphate (AMP)

52. Synthesis and Inactivation of Cyclic AMP

53. Fig. 6-8, p. 144 Adenylyl cyclase Phosphodiesterase cAMP

54. Cyclic AMP Activity Cyclic AMP activates protein kinase enzymes (such as protein kinase A) A protein is phosphorylated, its function is altered, and it triggers a chain of reactions leading to some response in the cell, such as a metabolic change The effect of the enzyme depends on the substrate

55. Signal Transduction: G Protein and Cyclic AMP

56. Fig. 6-9a, p. 144 Signaling molecule Extracellular fluid G protein Adenylyl cyclase Receptor Plasma membrane Cytosol 1

57. Fig. 6-9b, p. 144 Signaling molecule Receptor G protein separates Adenylyl cyclase 2

58. Fig. 6-9c, p. 144 Adenylyl cyclase activated Receptor Protein kinase A Phosphorylated protein Protein Alters some cell process 3

59. Summary: Second Messengers Signaling molecule (first messenger) binds to G protein– linked receptor Activates G protein Activates adenylyl cyclase Catalyzes formation of cAMP (second messenger) Activates protein kinase Phosphorylates proteins Response in cell

60. Summary: Second Messengers

61. Fig. 6-7, p. 143 Signaling molecule (first messenger) Extracellular fluid Adenylyl cyclase Receptor G protein Plasma membrane Cytosol cAMP Second messenger Protein Alters metabolism Affects gene activity Opens or closes ion channels 1 2 3

62. Phospholipids as Second Messengers Certain signal-receptor complexes activate a G protein that activates the membrane-bound enzyme phospholipase C Phospholipase C splits a membrane phospholipid, PIP 2 (phosphotidylinositol-4,5-bisphosphate), into two products, inositol trisphosphate (IP 3 ) and diacylglycerol (DAG) – both act as second messengers DAG (with calcium ions) in the plasma membrane activates protein kinase C enzymes IP 3 binds to calcium channels in the endoplasmic reticulum

63. Phospholipids as Second Messengers

64. Fig. 6-10, p. 145 Extracellular fluid Signaling molecule ReceptorPhospholipase C PIP 2 Activated protein kinase C G protein activated Protein Phosphorylated protein Ca 2+ Alters cell activity Alters cell activity 12 4 4 ER 3

65. Calcium Ions as Messengers Calcium ions (Ca 2+ ) have important functions in many cell processes, including neural signaling Calcium ions typically work by binding to certain proteins, (such as calmodulin) which then activate certain enzymes (such as protein kinases and protein phosphatases) Calmodulin helps regulate metabolism, muscle contraction, memory, inflammation, and apoptosis

66. Enzyme-Linked Receptors Activate Protein Kinase Signaling Pathways Many enzyme-linked receptors are tyrosine kinases that phosphorylate the amino acid tyrosine in proteins Signaling proteins bind to phosphorylated sites on receptor molecules, are phosphorylated, and can activate specific signaling pathways Activation of the last protein in the chain causes a specific cell response

67. Many Activated Intracellular Receptors are Transcription Factors Many intracellular receptors are transcription factors that regulate gene expression The ligand-receptor complex binds to a specific region of DNA and activates or represses specific genes Activated genes produce messenger RNA that carries the code for synthesis of a particular protein into the cytoplasm

68. Intracellular Receptors

69. Target cell Signaling molecules move through cytosol. 2 Signaling molecules pass through plasma membrane. 1 Signaling molecules Signaling molecules pass through nuclear envelope and combine with receptor in nucleus. 3 Nucleus Transcription factor (Activated receptor) DNA Activated receptor is a transcription factor that binds to and activates (or represses) specific genes. 4 Protein Messenger RNA Messenger RNA Ribosome Proteins are synthesized. 5 6 Cell activity is altered. Fig. 6-11, p. 146 Stepped Art

70. Scaffold Proteins Scaffold proteins organize groups of intracellular signaling molecules into signaling complexes Scaffold proteins position enzymes close to the proteins they regulate, and guide interactions between molecules, reducing cross-talk among different signaling pathways

71. A Scaffold Protein

72. Integrins Integrins are transmembrane proteins that transduce signals Specific signal transduction pathways are activated when signaling molecules bind to integrins in the plasma membrane

73. KEY CONCEPTS 6.4 In signal transduction, a cell converts an extracellular signal into an intracellular signal and relays the signal, leading to some change in the cell (the response)

74. 6.5 RESPONSES TO SIGNALS LEARNING OBJECTIVES: Describe three types of responses that cells make to signaling molecules Contrast signal amplification with signal termination

75. Three Types of Cellular Responses 1.Ion channels open or close Example: Neurotransmitters excite or inhibit other neurons or muscle cells by affecting ion channels 2.Enzyme activity is altered, leading to metabolic changes Example: Receptors on white blood cells (neutrophils) respond to peptides released by bacteria 3.Specific gene activity may be turned on or off Example: Some steroid hormones bind to nuclear receptors and directly regulate gene expression

76. The Response to a Signal is Amplified Signaling molecules are present in very low concentrations – the signal is amplified as it is relayed through a signaling pathway signal amplification A single signaling molecule can lead to changes in millions of molecules at the end of a signaling cascade

77. Signal Amplification: Epinephrine Epinephrine is released by adrenal glands in response to danger or other stress: Epinephrine binds to a G protein-linked receptor, activating a G protein Each G protein activates an adenylyl cyclase molecule Each adenylyl cyclase catalyzes the production of many cAMP molecules before it is inactivated Each cAMP molecule activates many molecules of a particular protein kinase Each protein kinase can phosphorylate many molecules of the next kinase in the pathway, and so on

78. Signals Must Be Terminated signal termination Returns the receptor and each of the components of the signal transduction pathway to their inactive states Examples: After a G protein is activated, a subunit of the G protein (GTPase) catalyzes the hydrolysis of GTP to GDP Cyclic AMP is inactivated by a phosphodiesterase, which converts it to adenosine monophosphate (AMP)

79. Signal Amplification

80. Fig. 6-15, p. 151 Receptor Signaling molecule G protein Adenylyl cyclase activated Protein kinase Protein Phosphorylated proteins 1 2 3 4 5 6

81. KEY CONCEPTS 6.5 The cell responds to signals by opening or closing ion channels; altering enzyme activity, which leads to metabolic changes and other alterations in cell activity; and by activating or inhibiting specific genes

82. 6.6 EVOLUTION OF CELL COMMUNICATION LEARNING OBJECTIVE: Cite evidence supporting a long evolutionary history for cell signaling molecules

83. Evolutionary History Some signal transduction pathways found in organisms as diverse as yeasts and animals are quite similar G proteins, protein kinases, and phosphatases are part of signaling pathways in most organisms Certain disease-causing bacteria have signal transduction pathways similar to those in eukaryotes Evidence suggests that cell communication first evolved in prokaryotes – some cell signaling molecules have been highly conserved (have not changed very much over time)

84. KEY CONCEPTS 6.6 Similarities in cell communication among diverse organisms suggest that the molecules and mechanisms used in information transfer evolved long ago